Pedigrees, karyotypes, and genetic disorders

CLE 3210.4.4 Compare different modes of inheritance: sex linkage, co-dominance,

incomplete dominance, multiple alleles, and polygenic traits.

CLE 3210.4.6 Describe the connection between mutations and human genetic disorders.

Overview

• Review karyotypes and chromosome type

• Discuss mutations and various genetic disorders

• Compare these with sex-linked inheritance

• Apply the use of karyotypes and pedigrees to better understand inheritance

Karyotypes• A karyotype is an organized profile of an individual’s

chromosomes. In a karyotype, chromosomes are arranged and numbered by size, from largest to smallest.

• Humans have 46 chromosomes or 23 pairs.

• 22 of these pairs are autosomes.

• 1 pair are sex chromosomes, X and Y.

• Which chromsomes do females have? Males?

3

Normal Karyotype

Autosomes

(44)

Sex chromosomes

(2)

Abnormal Karyotype

*3 Chromosomes instead of 2

Autosomes

(44)

Sex chromosomes

(2)

Mutations that produce changes in a single gene = _________________

Mutations that produce changes in whole chromosomes = _____________________

KINDS OF MUTATIONS

GENE MUTATIONS

CHROMOSOMAL MUTATIONS

Images from: http://www.bbc.co.uk/scotland/education/bitesize/higher/img/biology/genetics_adaptation/mutations/02gene_mutation.gif

KINDS OF MUTATIONS________ CELLS = ___________ CELLS

Somatic cell mutations can: ______________________

______________________

_____________

BODY

Cause cancer

Make cell not able to function

Kill cell

BUT _________ passed on to offspring

WON’T BE

SOMATIC

Kinds of Mutations

___________ = _________cells(sperm & eggs)

GAMETES

Germ cell mutations ________ passed on to offspring

CAN BE

http://anthro.palomar.edu/biobasis/images/meiosis.gif

GERM

MANY HUMAN GENES HAVE BECOME

KNOWN THROUGH THE STUDY OF GENETIC DISORDERS

Many genetic ___________ result fromchanges in the DNA code so

_________________ proteins are produced.

DISORDERS

NON-FUNCTIONING

http://patentdocs.typepad.com/photos/uncategorized/2007/05/28/dna1.gif

What do I need to know about each disorder?

• Which specific type of disorder it is:– Autosomal Recessive– Autosomal Dominant– Sex-Linked– Nondisjunction– Codominant

• What causes it• Characteristics of it

Autosomal Recessive Disorders

• A mutation that creates a disfunctional protein that appears RECESSIVE to the working allele.

• Includes:– Albinism– Cystic Fibrosis– Phenylketonuria (PKU)– Tay-Sach’s disease– Sickle-cell disease

• Example: Albinism:– AA = no albinism– Aa = carrier for

albinism– aa = albino

Autosomal Recessive Disorders

• Albinism– Characterized by lack of pigment in the

skin, hair, and eyes.

Albinism

Autosomal recessive: CYSTIC FIBROSIS CAUSE:

Loss of 3 DNA bases in a gene for the _____________ that transports _________ so salt balance is upset

Causes a build up of _________________ in lungs and digestive organs

.

thick mucous

protein

Image from: BIOLOGY by Miller and Levine; Prentice Hall Publishing ©2006

Cl- ions

Phenylketonuria (PKU)

CAUSE: Mutation in gene for an ___________ that __________ an ___________ called phenylalanine

Build up causes ________________________MENTAL RETARDATION

ENZYME

http://biology.clc.uc.edu/courses/bio104/protein.htm

breaks down amino acid

X

X

Phenylketonuria (PKU)

____ babies are ________for PKU before they leave the hospital.

Treatment: Need a diet _____________________ to extend life and ______________ mental retardation

If phenylalanine is an _____________, what type of foods should PKU patients avoid? __________________

amino acid

PROTEINS !

LOW in phenylalaninePREVENT

ALL tested

TAY-SACHS DISEASE___________________

CAUSE: Mutation in gene for an ___________ that breaks down a kind of _________in the developing _________

Build up of lipids in brain cells leads to:mental retardation, blindness, and DEATH in early childhood

Found more frequently in people with _______ _____________ ______________, ancestry

BRAIN

ENZYME

Jewish

Image from: http://www.djsfoundation.org/images/Steeler%20pics%20Dylan.jpg

AUTOSOMAL RECESSIVE

Mediterranean Middle Eastern

LIPID

Tay-Sachs

http://www.biochem.arizona.edu/classes/bioc460/spring/rlm/RLM36.1.html

A __________ person who carries a _________ allele for a genetic disorder, but ______________ the disorder themselves is called a_____________CARRIER

heterozygous

doesn’t show

recessive

A male who is a heterozygous carrier for an autosomal recessive disease marries a homozygous unaffected female. What is the chance of having an affected child? A child who is a carrier?

A. 50 %; 50%

B. 0%; 50%

C. 50%; 0%

D. 25%; 50%

20

A mutation that codes for a new proteinwhose action masks the normal alleleappears as a ______________ mutation.

Examples of _________________________ GENETIC DISORDERS:

____________________

____________________

DOMINANT

Huntington’s disease

Achondroplasia

AUTOSOMAL DOMINANT

HUNTINGTON’S DISEASE______________________

CAUSE: Extra 40-100 ______________ at end of gene on chromosome 4

The _____________ . . . the more __________ the symptoms.

severe

CAG repeats

http://www.healthsystem.virginia.edu/internet/huntdisease/images/cag.gif

more repeats

AUTOSOMAL DOMINANT

HUNTINGTON’S DISEASE

Causes progressive _____ of ________________ and ___________function

loss

muscle control

mental

1 in 10,000 people in U.S. have Huntington’s disease

http://www.scielo.br/img/revistas/bjmbr/v39n8/html/6233i01.htm

Huntington’s brain

Normal brain

A person with Huntington’s disease has a _____ chance of passing the disorder on totheir offspring.

Problem:Symptoms of disorder usually don’t show until ____________ . . .

so you don’t know you have it until ________ you have had children.

50%

MIDDLE AGE

AFTER

ACHONDROPLASIA(One kind of Dwarfism)

CAUSE: ___________________________ gene

200,000 “little people” worldwide

AUTOSOMAL DOMINANT

1 in 20,000 births

Mother has achondroplasia

Father has diastrophic displasia, a recessive disorder

Autosomal Dominant Disorders

• Achondroplasia– 99.96% of all the people in the world are

homozygous recessive for this trait (aa).– Interesting fact: The AA (homozygous

dominant) genotype of this trait is lethal and will result in a spontaneous abortion of the fetus.

• The only viable genotype is Aa.

Activity 1: With a partner

• Take 5 minutes and draw a two-circle Venn Diagram to compare and contrast:

• Autosomal recessive Vs. autosomal dominant

DISORDERS CAUSED BY ____________________

____________________SICKLE CELL DISEASE

CAUSE: T changed to A in gene for

__________________ (protein in red blood cells that carries oxygen in blood)

HEMOGLOBIN

AUTOSOMAL CODOMINANT ALLELES

SICKLE CELL DISEASE

SYMPTOMS:_____________ become sickle shaped in persons with ______ sickle cell ________

RED BLOOD CELLS

TWOALLELES

SICKLE CELL DISEASE

Circulatory problemsCells stick in capillariesLoss of blood cells (anemia)Organ damage (brain, heart, spleen)Can lead to DEATH

SICKLE CELL DISEASEMore common in _________________ 1 in 500 = have sickle cell disease 1 in 10 = carriers for allele

Also affects persons of _______________ and _________________ descent

Why do so many African Americans carry the sickle cell allele?

AFRICAN AMERICANS

MEDITERRANEANMIDDLE EASTERN

SICKLE CELL DISEASEMany can trace their ancestry to

westcentral Africa where ___________,a serious parasitic disease thatinfects red blood cells is common.

Images from: http://en.wikipedia.org/wiki/Malaria

MALARIA

A person who is __________________ for the ____________allele (ss) will have _______________

A person who is _________________ for normal hemoglobin alleles will have normal blood cells, but can become infected with __________ (SS)

A _________________ person (Ss)(with one normal/one sickle cell allele) isgenerally healthy and has the benefit ofbeing _________ to malaria

HOMOZYGOUSsickle cell

sickle disease

HOMOZYGOUS

malaria

HETEROZYGOUS

resistant

Chromosomes that determine the sex of an organism = _________________

All other chromosomes = _________________

Sex chromosomes

autosomes

Humans have two sex chromosomes

and _____ autosomes

X y44

http://www.angelbabygifts.com/

SEX DETERMINATIONXX =

Xy =

female

male

Who decides?

Mom can give X

Dad can give X or y

SO ____ determines sex of the baby.

If dad gives X with mom’s X = girlIf dad give y with mom’s X = boy

X X

X

y

X X X X

X y X y

Dad

Sex linked genes• In addition to their role in

determining sex of an organism, X and Y chromosomes have many other genes that are unrelated to sex.

• A gene on either sex chromosome is call a sex-linked gene.

• Congenital generalized hypertrichosis (CGH), the type that Danny Gomez has, is X-linked dominant; the gene that is mutated is found on the X chromosome.

• Sex-linked mutations can be either dominant or recessive.

37

X-linked inheritance pattern from a

heterozygote mother and unaffected father

_______________are diagrams that show how are ____________ on __________ over several generations

PEDIGREESgenes are passed

in families

Drawing a pedigree chart

http://www.beavton.k12.or.us/sunset/academics/genetics.htm

Genes carried on X or Y chromsomes= ___________________SEX LINKED TRAITS

These traits show up in different _______________ in males and females because they move with the sex chromosomes

percentages

Y-LINKED GENES: Genes ______________ chromosome

EXAMPLE:Hairy pinna

_________genes _____ show up _______Y linked in males

carried on Y

ONLY

____________ GENES: are carried on the X chromosome

X-linked recessive disorders show up _____________in ______ than femalesbecause males only have______ X chromosome.

MALES

X-LINKED

ONE

MORE frequently

Males ONLY HAVE ONE X

They eitherhave the disorder

DEFECTIVE NORMAL

They are normal

Or

FEMALES HAVE TWO X CHROMOSOMES

Females have one normalgene that works.

NORMAL DEFECTIVEDEFECTIVE

Females __________defective recessivealleles to show the disorder

need 2

Examples of ________________________ DISORDERS:

____________________

____________________

____________________

HEMOPHILIA

COLORBLINDNESS

DUCHENNE MUSCULAR DYSTROPHY

X-LINKED RECESSIVE

HEMOPHILIA CAUSE:

Mutation in genes for __________________ carried ______ chromosome

Blood clotting proteins are missing so person with this disorder can’t stop bleeding when injured; can ________________ from minor cuts or suffer internal bleedingfrom bruises or bumps.

bleed to death

Blood clotting proteinson X

COLORBLINDNESS CAUSE:

Mutation in one of three genes for _______________ carried on X chromosome

Persons with this disorder have trouble distinguishing colors.

_________________ colorblindness is most common

Seen in 1 in 10 males 1 in 100 females

Red-green

Color vision

http://gizmodo.com/gadgets/peripherals/samsung-develops-lcd-for-colorblind-036306.php

Duchenne Muscular DystrophyCAUSE: deletion in genethat codes for a_______________

Results in ____________________and loss of

___________________

http://www.cadenhead.org/workbench/gems/jerry-lewis-telethon.jpghttp://www.tokyo-med.ac.jp/genet/chm/dei.gif

muscle protein

progressive weakeningskeletal muscle

What’s the pattern: ________ traits show up _______ in _______

__________________ traits: ______________________ than females. ________________ can be ________.

_______________________ traits:BOTH ______ & _________ can be ________

Y-linked ONLY males

X-linked recessivemore common in males

AUTOSOMAL RECESSIVE

ONLY FEMALES carriers

MALES FEMALES carriers

Activity 2 (group): Interpreting pedigrees

• Using your pedigree reference sheet, try to identify the inheritance pattern for each pedigree on the handout.

• Is it:– Sex-linked dominant?– Autosomal dominant?– Autosomal recessive?

____________________________:Change in the ______________ or ____________ of chromosomes

CHROMOSOMAL MUTATIONS

structurenumber

Homologous chromosomes ________________ during MEIOSIS

= _________________________

One cell gets 2 copies of the chromosome the other cell gets none.

NONDISJUNCTION

fail to separate

Normal Meiosis Nondisjunction

http://www.tokyo-med.ac.jp/genet/anm/domov.gif

http://web.udl.es/usuaris/e4650869/docencia/gen_etica/meioferti2.html

Human Abnormalities caused by Non-Disjunction______________________________________________________

Down syndrome

Klinefelter syndrome

Turner syndrome

Down syndrome (= ____________)TRISOMY 21

Non-Disjunction Disorders• Down Syndrome (1:700)

– Characterized by obvious physical features and mild to profound mental disabilities.

• Short stature, heart defects, short lifespan, often sexually underdeveloped and sterile.

– Caused by a duplication of the 21st chromosome (47 TOTAL) = TRISOMY 21.

Turner syndrome – “monosomy”

Non-Disjunction Disorders• Turner’s Syndrome (1:5,000)

– THIS SYNDROME IS THE ONLY VIABLE MONOSOMY WHICH EXISTS IN HUMANS.

• 98% of these fetuses die prior to birth– Individuals affected with this disorder develop as

females only.– Occurs when all or part of one of the X chromosomes

is missing (45 TOTAL) =MONOSOMY X.– Characterized by short stature, webbed neck, stocky

build and absence of sexual development; normal intelligence.

Klinefelter syndrome XXy

Non-Disjunction Disorders• Klinefelter’s Syndrome

– A condition which occurs in males only.– Individuals with this disorder have an extra

X sex chromosome (47 TOTAL) = TRISOMY XXY.

– This disorder can affect the stages of language, physical, and social development.

– Characteristics include small testes, breast enlargement and other feminine body attributes; normal intelligence.

Which disorder is this?

Which disorder is this?

Which disorder is this?

Polygenic traits – Eye color

Compare and contrast

• Complete dominance

• Incomplete dominance

• Co-dominance

• Sex-linked