Biology 2250Biology 2250Principles of GeneticsPrinciples of Genetics

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Lab 4 Information: B2250 (Innes) webpageLab 4 Information: B2250 (Innes) webpage

download and print before lab.download and print before lab.

Virtual fly: log in and practiceVirtual fly: log in and practice

http://biologylab.awlonline.com/http://biologylab.awlonline.com/

Test 2 Test 2 Thursday Nov. 17Thursday Nov. 17http://http://webctwebct..munmun.ca:8900/.ca:8900/

All quizzes on WebCT for ReviewAll quizzes on WebCT for Review

Office Hours: 1:30 – 2:30 Tue, Wed., ThrOffice Hours: 1:30 – 2:30 Tue, Wed., Thr

or by appointment: 737-4754, dinnes@mun.caor by appointment: 737-4754, dinnes@mun.ca

Mendelian GeneticsMendelian Genetics

Topics:Topics: -Transmission of DNA during cell division-Transmission of DNA during cell division

Mitosis and MeiosisMitosis and Meiosis

- Segregation - Segregation

- Sex linkage (- Sex linkage (problem: how to get a white-eyed femaleproblem: how to get a white-eyed female))

- Inheritance and probability- Inheritance and probability

- Independent Assortment- Independent Assortment

- Mendelian genetics in humans- Mendelian genetics in humans

- Linkage- Linkage

- Gene mapping- Gene mapping

-Gene mapping in other organismsGene mapping in other organisms

(fungi, bacteria)(fungi, bacteria)

- Extensions to Mendelian Genetics- Extensions to Mendelian Genetics

- Gene mutation- Gene mutation

- Chromosome mutation- Chromosome mutation

(- Quantitative and population genetics)(- Quantitative and population genetics)

B2900B2900

Penetrance, expressivity Penetrance, expressivity and G X Eand G X E

PURPOSE: To provide a concise review for human cancer risk related to low-penetrance genes and their effects on environmental carcinogen exposure.

CONCLUSION: Sporadic cancers are caused by gene-environment interactions rather than a dominant effect by a specific gene or environmental exposure.

MutationMutation

Source of genetic variation:Source of genetic variation:

Gene Mutation (Phenotypic effects) Gene Mutation (Phenotypic effects)

- somatic, germinal- somatic, germinal

Chromosome mutations (Ch. 11 prob. 1, Chromosome mutations (Ch. 11 prob. 1, 2)2)

- structure - structure

- number - number

MutationMutation

Gene Mutation:Gene Mutation:

aa++------>a Forward mutation------>a Forward mutation

aa ------>a------>a++ Reverse mutation Reverse mutation

1. Somatic mutation1. Somatic mutation

- not transmitted to progeny- not transmitted to progeny

2. Germinal Mutation2. Germinal Mutation

- transmitted to next generation- transmitted to next generation

Somatic MutationsSomatic Mutations

Petal colour:Petal colour:Rr Rr redredrr whiterr white

Plant genotype: RrPlant genotype: Rr mutation: Rr rrmutation: Rr rr

Somatic mutationsSomatic mutations

Germinal mutationsGerminal mutations

AA (blue)AA (blue)

mutationmutation

Aa Aa self self aa(white)aa(white)

Mutant PhenotypesMutant Phenotypes

Morphological Morphological

LethalLethal

Biochemical Biochemical

ResistanceResistance

Conditional - DTSConditional - DTS (David T. Suzuki) (David T. Suzuki)

(permissive and restrictive conditions)(permissive and restrictive conditions)

Mutation FrequencyMutation Frequency

Drosophila Drosophila eye-colour weye-colour w++ w 4 x 10 w 4 x 10-5-5 per gamete per gamete

Humans Hemophilia (X-linked recessive) 4 x 10Humans Hemophilia (X-linked recessive) 4 x 10-5-5 per gamete per gamete

(1 in 25,000)(1 in 25,000)

““It is estimated that up to 30% of cases of hemophilia have It is estimated that up to 30% of cases of hemophilia have no known family history. Many of these cases are the no known family history. Many of these cases are the result of new mutations. This means that hemophilia can result of new mutations. This means that hemophilia can affect any family.”affect any family.”

Mutation FrequencyMutation Frequency

Drosophila Drosophila eye-colour weye-colour w++ w 4 x 10 w 4 x 10-5-5 per gamete per gamete

Mutation rate for a particular gene: very low (efficient repair)Mutation rate for a particular gene: very low (efficient repair)

but,but,

Large number of genes in a genome: mutations occur every Large number of genes in a genome: mutations occur every generationgeneration

4 x 104 x 10-5-5 x 50,000 genes = 2 mutations x 50,000 genes = 2 mutations

Gene MutationGene Mutation

Mutations are rare and randomMutations are rare and random

Ultimate source of genetic variationUltimate source of genetic variation

Cancer: Proto-oncogene Cancer: Proto-oncogene oncogene oncogene cancer cancer

mutationmutation

“…“…in an oncogene mutation, the activity of the mutant oncoprotein has been in an oncogene mutation, the activity of the mutant oncoprotein has been uncoupled from its normal regulatory pathway, leading to its continuous uncoupled from its normal regulatory pathway, leading to its continuous unregulated expression.” unregulated expression.” tumor growth tumor growth

Chromosome MutationsChromosome Mutations

Gene mutationGene mutation: : detected geneticallydetected genetically

Chromosome MutationsChromosome Mutations: detected genetically and: detected genetically and

cytologicallycytologically

1. Structure1. Structure

2. Number2. Number

Chromosome MutationsChromosome Mutations

1. Structure Ch. 11 363 – 3721. Structure Ch. 11 363 – 372

2. Number Ch. 11 p. 350 - 3632. Number Ch. 11 p. 350 - 363

1. Chromosome Structure1. Chromosome Structure

Karyotype:Karyotype:

1. size and number1. size and number

2. centromere position:2. centromere position:

telocentrictelocentric

acrocentricacrocentric

metacentricmetacentric

submetacentricsubmetacentric

acentricacentric (lost)(lost)

Chromosome StructureChromosome Structure

33. Heterochromatin pattern. Heterochromatin pattern

- heterochromatin- heterochromatin (dark) (dark)

- euchromatin- euchromatin (light) (light)

44. Banding patterns:. Banding patterns:

a) staining a) staining Giemsa bandsGiemsa bands

b) polytene chromosomes (flies)b) polytene chromosomes (flies)

G-bandsG-bands

Paint of Chr-22Paint of Chr-22

““Paint”Paint”

Structural AbnormalitiesStructural Abnormalities Normal a b c d e fNormal a b c d e f

1. Deletion a c d e f1. Deletion a c d e f

2. Duplication a b b c d e f2. Duplication a b b c d e f

3. Inversion a e d c b f3. Inversion a e d c b f

4. Translocation4. Translocation

a b c d j k g h i e fa b c d j k g h i e f

Structural AbnormalitiesStructural Abnormalities

1. Deletions:1. Deletions:

deletion homozygote---->usually lethaldeletion homozygote---->usually lethal

deletion heterozygote----> viabledeletion heterozygote----> viable

deletion loop deletion loop bb

(pairing of(pairing of a c d a c d

homologues)homologues) a c d a c d

deletiondeletion

Deletion heterozygoteDeletion heterozygote

deletion loopdeletion loop

PseudodominancePseudodominance

Deletion Heterozygote:Deletion Heterozygote:

deletion loop deletion loop bb

(pairing of(pairing of a c d a c d

homologues)homologues) + + + + + +

deletiondeletion

Phenotype:

+ b + ++ b + +

Deletion MappingDeletion Mapping

Prune pn

Structural AbnormalitiesStructural Abnormalities

Deletion:Deletion: notch-wing ( notch-wing (DrosophilaDrosophila))

PhenotypePhenotype

GenotypeGenotype wing survivalwing survival

NN+ + NN++ normal alive normal alive

NN++ N notch alive N notch alive

N N - deadN N - dead

(recessive lethal)(recessive lethal)

Genetics of DeletionsGenetics of Deletions

• Reduced map distance ( chromosome Reduced map distance ( chromosome shortened)shortened)

• Recessive lethalRecessive lethal• Deletion loop (detected during meiosis)Deletion loop (detected during meiosis)

Structural AbnormalitiesStructural Abnormalities

2. Duplications:2. Duplications:

tandem duplicationtandem duplication

a b b c da b b c d

maintain original evolve newmaintain original evolve new

function functionfunction function

deletiondeletion

Tandem duplicationTandem duplication

Unequal crossing overUnequal crossing over

Bar Eye Mutation (Dominant) Bar Eye Mutation (Dominant)

Gene Duplication Gene Duplication and Evolutionand Evolution

Gene duplication - Evolution of new functionGene duplication - Evolution of new function

Example: Hemoglobin genes - duplicationExample: Hemoglobin genes - duplication

Express in different stages:Express in different stages:

embryo – fetus – adult embryo – fetus – adult

Hemoglobin:

Alpha

Beta

Gamma

………..

Structural AbnormalitiesStructural Abnormalities

3. Inversions - different gene order3. Inversions - different gene order

- usually viable- usually viable

a b c d e f a b e d c f a b e d c fa b c d e f a b e d c f a b e d c f

a b c d e f a b c d e f a b e d c fa b c d e f a b c d e f a b e d c f

homozygote heterozygote homozygotehomozygote heterozygote homozygote

N N N I I IN N N I I I

normal (N) inversion (I)normal (N) inversion (I)

Cytological consequences of an InversionCytological consequences of an Inversion

Heterozygote: Heterozygote: Inversion LoopInversion Loop

a b c d ea b c d e

a d c b ea d c b e

X

crossovercrossover

Inversion Loop

Fig. 11-21

Cytological consequences of an InversionCytological consequences of an Inversion

Heterozygote: Heterozygote: Inversion LoopInversion Loop

Cross-over within Cross-over within an an inversioninversion

dicentric bridge (broken)dicentric bridge (broken)

acentric fragment (lost)acentric fragment (lost)

deletionsdeletions

Inversion Inversion heterozygoteheterozygotewith crossing with crossing overover

Fig. 11-22

Inversion HeterozygoteInversion Heterozygote

• Reduced recombination frequencyReduced recombination frequency

(suppression of crossing over)(suppression of crossing over)

• SemisterileSemisterile

4. 4. TranslocationTranslocation

a b c d j k g h i e fa b c d j k g h i e f

Translocation HeterozygoteTranslocation Heterozygote (meiosis) (meiosis)

NN11

TT22TT11

NN22

TranslocationTranslocation

TranslocationTranslocation heterozygoteheterozygote

Fig. 11-24

Translocation heterozygoteTranslocation heterozygoteAdjacent segregationAdjacent segregation

T1

N1

N2

T2

inviableinviable

Translocation heterozygoteTranslocation heterozygoteAlternate segregationAlternate segregation

T1

N1 N2

T2

viableviable

TranslocationTranslocation

Change linkage relationshipsChange linkage relationships

(position effects)(position effects)

Change chromosome sizeChange chromosome size

Semisterile - unbalanced meiotic productsSemisterile - unbalanced meiotic products

normalnormal

abortedabortedCorn PollenCorn Pollen

Structural AbnormalitiesStructural Abnormalities Normal a b c d e fNormal a b c d e f

1. Deletion a c d e f1. Deletion a c d e f

2. Duplication a b b c d e f2. Duplication a b b c d e f

3. Inversion a e d c b f3. Inversion a e d c b f

4. Translocation4. Translocation

a b c d j k g h i e fa b c d j k g h i e f

Human Chromosomes

MutationMutation

Source of genetic variation:Source of genetic variation:

Gene Mutation Gene Mutation

- somatic, germinal- somatic, germinal

Chromosome mutations (Ch. 11)Chromosome mutations (Ch. 11)

- structure - structure

- number- number

Chromosome MutationChromosome Mutation(2. changes in number)(2. changes in number)

Euploidy: Euploidy: variation in complete sets ofvariation in complete sets of

chromosomeschromosomes

Aneuploidy: Aneuploidy: variation in parts of chromosomevariation in parts of chromosome

setssets

EuploidyEuploidy

1x 1x monoploid (1 set) = n monoploid (1 set) = n

2x 2x diploid (2 sets) = 2ndiploid (2 sets) = 2n

3x triploid3x triploid

4x tetraploid4x tetraploid

5x pentaploid 5x pentaploid polyploid (> polyploid (> 22 sets) sets)

6x hexaploid6x hexaploid

n = # chromosomes n = # chromosomes

in the gametesin the gametes

PolyploidsPolyploids

Autopolyploids: Autopolyploids: within one specieswithin one species

Allopolyploids: Allopolyploids: from different, closelyfrom different, closely

related speciesrelated species

PolyploidsPolyploids

Larger Larger than Diploidsthan Diploids

PolyploidsPolyploids

Triploids: = 3nTriploids: = 3n

- problems with pairing during- problems with pairing during

meiosismeiosis

- unbalanced gametes- unbalanced gametes

- usually steril- usually sterilee

Applications:Applications: seedless fruits, sterile fish seedless fruits, sterile fish

aquacultureaquaculture

Formation of TriploidsFormation of Triploids

nn

nn

nn

= = 3n3n

nn

PolarPolarbodiesbodies

nn 22nnnn

= = 3n3n

Triploids (3x)Triploids (3x)

Why can’t a triploid produce viable Why can’t a triploid produce viable gametes ?gametes ?

Fig. 11-5

Triploids (3x)Triploids (3x)

x = 1x = 1 GametesGametes

TriploidsTriploids

x = 2x = 2

GametesGametes

oror

viableviable

Non-Non-viableviable

TriploidsTriploids

Probability (2x or x gamete) =Probability (2x or x gamete) =

( )( )if x = 10 Prob. = 0.002 of viable gametesif x = 10 Prob. = 0.002 of viable gametes

11

22

x - 1x - 1

AutotetraploidAutotetraploid

AutotetraploidAutotetraploid

Doubling of chromosomes: 2x----> 4xDoubling of chromosomes: 2x----> 4x

Even number of chromosomes: normal meiosisEven number of chromosomes: normal meiosis

2<---->2 segregation------> functional 2<---->2 segregation------> functional gametesgametes

Triploid

2n = 42 x = 7

n = 21

2n = 14, n = x = 7

Chromosome sets:

A, B, D

7 7 7

hybrid

Origin of Origin of WheatWheat

Fig. 11-10Fig. 11-10

2n = 28

n = 14

77 1414

AllopolyploidAllopolyploid

PolyploidyPolyploidy

Plants: Plants: speciation speciation

Animals: Animals: - rare (sex determination)- rare (sex determination)

- fish- fish (salmon) (salmon)

- - parthenogenetic parthenogenetic animalsanimals

123 11 22 12 12

Latitute North

30 40 50 60 70 80 90

% P

olyp

loid

s

30

40

50

60

70

80

90Plant PolyploidsPlant Polyploids

Chromosome MutationChromosome Mutation((changes in number)changes in number)

Euploidy: Euploidy: variation in complete sets ofvariation in complete sets of

chromosomeschromosomes

Aneuploidy: Aneuploidy: variation in parts of chromosomevariation in parts of chromosome

setssets

AneuploidyAneuploidy

Nullisomics (2n - 2)Nullisomics (2n - 2)

Monosomics (2n - 1)Monosomics (2n - 1)

Trisomics (2n + 1)Trisomics (2n + 1)

AneuploidyAneuploidy

Nullisomics (2n - 2)Nullisomics (2n - 2)

- lethal in diploids- lethal in diploids

- tolerated in polyploids- tolerated in polyploids

Monosomics (2n - 1)Monosomics (2n - 1)

- disturbs chromosome balance- disturbs chromosome balance

- recessive lethals hemizygous- recessive lethals hemizygous

Trisomics (2n + 1)Trisomics (2n + 1)

- sex chromosomes vs autosomes- sex chromosomes vs autosomes

- size of chromosome- size of chromosome

AneuploidyAneuploidy

Non-disjunction: GametesNon-disjunction: Gametes

Meiosis I n + 1 n - 1Meiosis I n + 1 n - 1

Meiosis II n + 1 n - 1 Meiosis II n + 1 n - 1 nn

n x n - 1 ---------> 2n - 1 monosomicn x n - 1 ---------> 2n - 1 monosomic

n x n + 1 ---------> 2n + 1 trisomicn x n + 1 ---------> 2n + 1 trisomic

AneuploidyAneuploidyHumans:Humans: (live births) (live births)

Monosomics - XO Turner syndromeMonosomics - XO Turner syndrome

- no known autosomes- no known autosomes

Trisomics XXY Trisomics XXY KKlinefelter sterile malelinefelter sterile male

XYY fertile maleXYY fertile male ( X or Y gametes)( X or Y gametes)

XXX sometimes normalXXX sometimes normal

21 Down21 Down

18 Edwards syndromes18 Edwards syndromes

13 Patau13 Patau

G-bandsG-bands

13 1821 X Y

Maternal Age (years)

20 25 30 35 40 45 50

Dow

ns B

irths

per

100

0

0

5

10

15

20

25Downs Births per 1000Downs Births per 1000

Mutations Causing Death and Mutations Causing Death and Disease in HumansDisease in Humans

% of live births% of live births

Gene mutations: Gene mutations: 1.2 1.2

Chromosome mutationsChromosome mutations:: 0.610.61

Chromosome MutationsChromosome Mutations(Humans)(Humans)

% of spontaneous abortions% of spontaneous abortions

Trisomics 26 %Trisomics 26 %

XO 9 %XO 9 %

Triploids 9 %Triploids 9 %

Tetraploids 3 %Tetraploids 3 %

Others 3 %Others 3 %

Chromosome 50 %Chromosome 50 %

abnormalitiesabnormalities

Chromosome MutationsChromosome Mutations

Comparison of euploidy with aneuploidyComparison of euploidy with aneuploidy

Aneuploids more abnormal than euploids:Aneuploids more abnormal than euploids:

likely due to gene imbalancelikely due to gene imbalance

Plants more tolerant than animals to Plants more tolerant than animals to aneuploidy and polyploidyaneuploidy and polyploidy

(animal sex determination)(animal sex determination)

SummarySummaryMutationMutation - gene - gene

- chromosome- chromosome

(structure, number)(structure, number)

DetectingDetecting - cytology - cytology

- phenotype- phenotype

Rate of mutationRate of mutation - low - low

MutationMutation - source of genetic variation - source of genetic variation

- evolutionary change- evolutionary change

geneticgeneticanalysisanalysis

Chapter Chapter ReferencesReferences

RRecombinationecombination, l, linkage mapsinkage mapsCh. 6 p. 148 – 165 Prob: 1-5, 7, 8, 10, 11, 14Ch. 6 p. 148 – 165 Prob: 1-5, 7, 8, 10, 11, 14

Extensions to Mendelian GeneticsExtensions to Mendelian Genetics

Ch. 14 p. 459 – 473 Prob: 2, 3, 4, 5, 6, 7Ch. 14 p. 459 – 473 Prob: 2, 3, 4, 5, 6, 7

Chromosome MutationsChromosome Mutations

Ch. 11 p. 350 – 377 Prob: 1, 2Ch. 11 p. 350 – 377 Prob: 1, 2

Mendelian GeneticsMendelian Genetics

Topics:Topics: -Transmission of DNA during cell division-Transmission of DNA during cell division

Mitosis and MeiosisMitosis and Meiosis

- Segregation - Segregation

- Sex linkage (- Sex linkage (problem: how to get a white-eyed femaleproblem: how to get a white-eyed female))

- Inheritance and probability- Inheritance and probability

- Independent Assortment- Independent Assortment

- Mendelian genetics in humans- Mendelian genetics in humans

- Linkage- Linkage

- Gene mapping- Gene mapping

-Gene mapping in other organismsGene mapping in other organisms

(fungi, bacteria)(fungi, bacteria)

- Extensions to Mendelian Genetics- Extensions to Mendelian Genetics

- Gene mutation- Gene mutation

- Chromosome mutation- Chromosome mutation