Exam #2 W 7/9 in class Today: Development and Genome Organization.

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Transcript of Exam #2 W 7/9 in class Today: Development and Genome Organization.

Exam 2 W 79 in class

Today Development and Genome Organization

Development differentiating cells to become an organism

Cells function differently because they express differentgenes

The proper control of gene expression is critical for proper development

So development in animals is one way

Inverse relationship between smoking and weight more smoking less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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  • Slide 109

Development differentiating cells to become an organism

Cells function differently because they express differentgenes

The proper control of gene expression is critical for proper development

So development in animals is one way

Inverse relationship between smoking and weight more smoking less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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Cells function differently because they express differentgenes

The proper control of gene expression is critical for proper development

So development in animals is one way

Inverse relationship between smoking and weight more smoking less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

The proper control of gene expression is critical for proper development

So development in animals is one way

Inverse relationship between smoking and weight more smoking less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

So development in animals is one way

Inverse relationship between smoking and weight more smoking less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Inverse relationship between smoking and weight more smoking less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What is the connection

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 109

Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Adults metabolism may react to poor nutrition as fetuseshellip

Adaptation of Thriftiness

or

Catch Up Growth

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
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  • Slide 105
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  • Slide 107
  • Slide 108
  • Slide 109

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 101
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 105
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  • Slide 107
  • Slide 108
  • Slide 109

Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth

Study of babies born during Dutch famine of 1944-45hellip

20 years later found that these babies had higher rates of obesity

Precise mechanism is not known

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 89
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  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

For Momrsquos who abstained during pregnancy no effect on fetus or as adult

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What about smoking

17000 births studied and checked at age 16 and 33

Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity

Smoking during first trimester had same effect as during whole pregnancy

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What about smoking

For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What about smoking

Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 60
  • Slide 61
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  • Slide 93
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  • Slide 97
  • Slide 98
  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

Nicotine can inhibit hunger and increase energy expenditure

This can lead to poor fetal nutrition

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

AAL 388

Mammalian circulation

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Nicotine causes blood vessels to constrict

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

CO in blood decreases delivery of O2 to fetus

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip

Nicotine can inhibit hunger and increase energy expenditure

Nicotine causes constriction of blood vessels and may limit blood flow to the fetus

CO in blood decreases delivery of O2 to fetus

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 5
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Hormones are molecules produced in one cell and signal another

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 11
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  • Slide 50
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  • Slide 94
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  • Slide 96
  • Slide 97
  • Slide 98
  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why

Nicotine and other toxins in smoke may directly affect hormones that direct fetal development

Including hormones that direct brain development

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

So

Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 42
  • Slide 43
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  • Slide 50
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  • Slide 91
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  • Slide 93
  • Slide 94
  • Slide 95
  • Slide 96
  • Slide 97
  • Slide 98
  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Correlation of weight (BMI)

Identical twins reared together 80

Identical twins reared apart 72

Fraternal twins reared together 43

Biological siblings 34

Parents and children living together 26

Adopted children and parents 4

Unrelated children living together 1

Correlation of weight and relatedness

The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)

Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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Nature and Nurture

Are traits coded for by genes fixed while traits coded for by the environment are under our control

So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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So development in animals is one way

Why

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Fig 233

Developmental mutants of Drosophila melanogaster

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
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  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Vertebrate Development

from zygote to adult

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Early embryo developmentFig 1913

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 77
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  • Slide 83
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  • Slide 86
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  • Slide 88
  • Slide 89
  • Slide 90
  • Slide 91
  • Slide 92
  • Slide 93
  • Slide 94
  • Slide 95
  • Slide 96
  • Slide 97
  • Slide 98
  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Totipotent ability to differentiate into any cell-type

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
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  • Slide 6
  • Slide 7
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  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Totipotency is limited to early stages of animal development

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why do cells lose totipotency

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 21
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  • Slide 96
  • Slide 97
  • Slide 98
  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why do cells lose totipotency

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Mature differentiated plant cells are totipotent

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
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  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why do cells lose totipotency

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

bullGene expression can be controlled at many points between DNA and making the final proteins

bullChanges in the various steps of gene expression control when and how much of a product are produced

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged

Fig 1021

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Normally DNA is loosely packaged

During mitosis DNA is tightly packaged as chromosomes and

individually visible

Fig 38

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible

Fig 1021

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Irreversible packaging of DNA partially explains the loss of totipotency

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Stem cells still have totipotencyFig 1913

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 97
  • Slide 98
  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Embryonic Stem Cells are totipotent

Adult Stem Cells are pluripotent (only form some cell types)

Fig 1914

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

What genetic mechanisms regulateallow development

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Increases in cell number play a

rolehellip

Fig 231

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

hellipso does cell death

Fig 231

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 109

CB 2119

Development of a mouse paw yellow areas show dying cells

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

All humans are female for the first nine weeks of development

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Fig 2327

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

All humans are female for

the first nine weeks of

development

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Each whorl expresses a specific combination of three genes

Fig 2324

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Fig 2323

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Changing expression of A B or C genes

changes organ identity

Fig 2324

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Flower partsComplexity from a few simple genes

4 whorls of a flowerFig 2323

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

How does a cell know where it is

Fig 232

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
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  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Drosophila Development

Fig 234

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 107
  • Slide 108
  • Slide 109

Polarity development by mRNA localization

Fig 235

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Hox genes regulate the identity of body parts Fig 2311

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
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  • Slide 101
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Expression of hox genes in the embryo give rise to different adult body parts

embryo

adult

Fig 2311

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)

Fig 2316

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Many hox proteins have common sequences(these are from Drosophila)

Fig 2313

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 99
  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

helix-turn-helix a common DNA-binding motif

Fig 2313

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Many developmental genes are transcription factors

these are from Drosophila

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Reporter gene

protein

coding region

promoter reporter gene (luciferase etc)

easily visualized protein

promoter

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
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  • Slide 100
  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop

ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218

Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
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Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 107
  • Slide 108
  • Slide 109

The order of Hox genes parallels the order of body parts in which they are expressed

Fig 2317

25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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25000 12

How are genomes organized Tbl 202

httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]

Map of human chromosome 20

How does the organization of a genome affect its function

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
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  • Slide 107
  • Slide 108
  • Slide 109

Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)

Comparison of Fugu and human huntingtin gene

75 X bigger

both have 67 exons connected by lines

(green indicates transposons prevalent in human version)

(puffer fish)

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 107
  • Slide 108
  • Slide 109

Some genes have several similar sequences within the genome known as a gene family

Fig 87

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans

Fig 87

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 105
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  • Slide 107
  • Slide 108
  • Slide 109

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 107
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Fetal Hb binds O2 more strongly than maternal Hb

Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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Pseudogenes have the structure of a gene but are not expressed

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 109

Most cells in an organism have the same DNAWhich cells have different DNA

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

DNA is rearranged in B-cells during antibody production

Fig 179

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Each B-cell produces a unique antibody

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

DNA rearrangements in B-cells allow each B-cell to produce a unique antibody

Fig 179

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Transposons mobile DNA

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Transposons comprise much of human DNA

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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  • Slide 6
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  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Fig 1712C

Retro-transposons move via an RNA intermediate

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
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  • Slide 6
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  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
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  • Slide 101
  • Slide 102
  • Slide 103
  • Slide 104
  • Slide 105
  • Slide 106
  • Slide 107
  • Slide 108
  • Slide 109

Humans and chimpanzees shared a common ancestor about 6 million years ago

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
  • Slide 3
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QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

human

chimp

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Humans have more transposons than chimps

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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  • Slide 109

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 109

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

What affect do transposons have in humans

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Does transposition cause disease

An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
  • Slide 2
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Diseases caused by transposon insertion

bullDuchenne muscular dystrophy

bullCoffin-Lowry syndrome

bullFukuyama-type congenital muscular dystrophy (FCMD)

bullcolon cancer

bullchronic granulomatous disease

bullX-linked dilated cardiomyopathy

bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

bullneurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births

Which transposons are mobile

Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191

Which transposons are mobile

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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  • Slide 109

QuickTimetrade and aTIFF (Uncompressed) decompressor

are needed to see this picture

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans

Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

  • PowerPoint Presentation
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Conclusions

bullTransposons may play a role in evolution

bullMore abundant transposons in humans show ldquorecentrdquo transposon activity

bullTransposons are still active and can cause mutations and disease

Exam 2 W 79 in class

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Exam 2 W 79 in class

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