1

Identifying Genes and Defining Alleles

Mutant Hunt - independently isolate number of mutants

with identical phenotypes - verify mutant phenotype is recessive - establish pure-breeding strain for each

How many genes are involved? The same gene for all strains? Different genes for different strains?

2

Identifying Genes and Defining Alleles

Mutant Hunt Ex. White flowers in plant species with purple flowers Mutant strain 1 - isolated in Australia Mutant strain 2 - isolated in Pennsylvania

3

Identifying Genes and Defining Alleles

Biochemical basis for white flower color

If only one gene involved: (A or a alleles) Enzyme AWhite pigment Purple pigment

If two different genes involved: (Aa and Bb) Enzyme A Enzyme BWhite White Purple pigment

4

Identifying Genes and Defining Alleles

Complementation Test - One gene or Two genes?

Cross recessive pure-breeding strains with same(or related) phenotype to each other.

If F1 progeny are all mutant = one gene (two alleles)

If F1 progeny are wild type = two different genes

5

Identifying Genes and Defining Alleles

Complementation Test - One gene or Two genes?

Alleles of the same gene

6

Identifying Genes and Defining Alleles

Complementation Test - One gene or Two genes?

7

Complementation Analysis

Independently isolated mutants - all same phenotype Cross in all possible combinations

+ wild-type offspring (complementation) - mutant offspring

How many genes?

Which mutantsare defective in same gene?

8

Multiple Alleles

Many different forms of the same gene

9

Multiple Alleles

Example

Cross A x BAnything possible

10

Multiple Alleles

Example

w gene

wild-type,white,eosinalleles

11

Multiple Alleles

12

Multiple Alleles

Humans are highly polymorphic Ex. >200 different alleles for cystic fibrosis gene Ex. >390 alleles for human leukocyte antigen (HLA)

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Dominance of Alleles

Complete Dominance / Complete Recessiveness

Phenotype: Dominant RecessiveGenotype: AA, Aa aa

Haplo-Sufficient

Loss ofFunction

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Dominance of Alleles

Incomplete Dominance (Semidominance)

Haplo-insufficient

15

Dominance of Alleles

Co-dominance

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Dominance of Alleles

Sickle cell anemia

17

Lethal Genes

Dominant lethal: L- (LL or Ll) doesn’t survive, rare

Ex. Huntington chorea - neurodegenerative, late onset

Recessive lethal: ll homozygotes die

Ex. Achondroplastic dwarfism

a+a+ normal a+ ad dwarf ad ad die in utero

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Examples of Recessive Lethal Genes

Creeper Chickens: Autosomal lethal

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Examples of Recessive Lethal Genes

2:1 ratio

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Subvital Genes

Survival of genotype is not as good as normal

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Gene Interactions & Modified Ratios

Variations of Mendelian Dihybrid Ratios: Two genes involved

A- B- aaB- A-bb aabb

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Gene Interactions & Modified Ratios

Comb shapes

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Gene Interactions & Modified Ratios

Bateson & Punnett crossed purebreeding chickens

How many genes are involved?

24

Gene Interactions & Modified Ratios

25

Gene Interactions & Modified Ratios

9:3:3:1

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Gene Interactions & Modified Ratios

Flower Color in Sweet Peas - Complementation

9:7 ratio

27

Gene Interactions & Modified Ratios

Fruit shape in summer squash

9:6:1 ratio

28

Epistasis

One gene masks the expression of another gene

aa B- A- B-

Recessive Dominant

Gene masking other = epistatic

Gene being masked = hypostatic

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Recessive Epistasis

Ex. Coat color in mice

C- color, cc none A- pattern, aa none

9:3:4ratio

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Recessive Epistasis

Ex. Coat color in Labrador retrievers

EeBb x EeBb 9/16 black: 3/16 brown:4/16 yellow

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Dominant Epistasis

Ex. Fruit color in summer squash

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Dominant Epistasis

Ex. Fruit color in summer squash

Hypothetical pathway

ww

ww

Y-

yy

33

Dominant Epistasis

Ex. Graying in horses

4 years

7 years

34

Gene Interactions: Eye Color in Drosophila

bw+ bw st+ st w+ w

bw+ bw st+ st w+ w

bw+ - st+ - w+ -

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Gene Interactions: Eye Color in Drosophila

bw+ bw st+ st w+ w X bw+ bw st+ st w+ w

bw+- st+- w+-

bw+- st+- ww

bw+- stst w+-

bwbw st+- w+-

bw+- stst ww

bwbw st+- ww

bwbw stst w+-

bwbw stst ww

36

Suppression

Second gene blocks mutant phenotype caused by first gene

Normal plant - no malvidin; K- malvidin, kk none; D- suppresses K-, dd no suppression

13:3 ratio

37

Modifier Gene

Second gene affects degree of expression of first gene

Ex. dark color versus light color

B- black, bb brown D- intense color, dd dilute color

9:3:3:1 ratio

38

Duplicate Genes

Both genes control the same cellular activity

Ex. A1- or A2 - round fruit a1a1 and a2a2 narrow fruit

Enz A1narrow round

Enz A2

A1a1 A2a2 x A1a1 A2a2

9/16 A1- A2-: 3/16 A1- a2a2: 3/16 a1a1 A2-: 1/16 a1a1 a2a2

15 : 1 ratio of round : narrow

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Pleiotropic Genes

One gene has many effects on the phenotype

Ex. Cystic fibrosis - recessive allele, autosomal gene defective calcium transportbreathing difficultiesdigestive problemsreproductive deficienciesreduced immunity

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Penetrance

Percentage of individuals with certain genotype who express the expected phenotype.

brachydactyly

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Expressivity

Degree or extent to which a given genotype is expressed.

Variations may result from:environmentgenetic backgroundother factors

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Variable Expressivity

Spotting in dogs

All have the same genotype

43

Variable Expressivity

Neurofibromatosis

café au lait spots

freckling

neurofibromas

44

Penetrance and Expressivity

45

Monogenic vs Quantitative Traits

Discontinuous traits Continuous traits

AA Aa aa aabbccdd AABBCCDD As gene number increases, phenotype distribution approaches normal curve

46

Quantitative Genetics

Polygenic - Many genes affect one aspect of phenotype

Quantitative traits - each allele of each gene contributes equally

Ex. height, weight, skin color

47

Quantitative Genetics

Two genes contributing to phenotype quantitatively

F2 ratio

1:4:6:4:1

48

Quantitative Genetics

Inheritance of ear length in corn

F1 mean =intermediate

More variabilityin F2