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Exam IIThursday 28 Feb 2013

Coverage: All material since last examLecture 5: Sex-linkage part (incl. XX/XY, ZZ/ZW, etc.)Lecture 6: Linkage (incl. repulsion/coupling)Lecture 7: LOD score analysisLecture 8: Gene Interactions I (incl. codominance)Lecture 9: Gene Interactions II (incl. epistasis)

Problems/Quizzes:1) Chi2 Problem Set 2) Sex-linkage Problem Set (incl. sex/auto mix)3) Linkage Problem Set4) Complementation Problem Set>Lod Score (Lab worksheet)>Mode of Inheritance (F1/F2 analysis Lab assignment)>Quizzes: Sex-linkage (Q2); Linkage (Q3)

Chapter 4Allele and Gene Interactions II

Part II: The environment, penetrance, expressivity, and epistasis

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Usually you expect an individual with a specific genotype to show expected phenotype:

Example: For flower color: w = recessive white allele

W = dominant purple allele

Expect: ww = white; Ww and WW = purple

è However, in some cases Ww or WW might be white

Factors that may affect expression of trait:

1. Physical Environment2. Genetic Environment3. Penetrance of trait4. Expressivity of trait

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Influence of the Environment on Gene Expression

Physical Environment à can have effect on expression of genes1) Temperature

Ex.: Drosophila shibire mutation à recessive temperature sensitive mutationà affects formation of vesicles that transmit signals

between nerve cells‘Permissive’ temperature: • 25C

-flies are viable and fertile

Sh

Shmonohybrid F2

sh*

sh*

ShSh

Shsh*

Shsh*

sh*sh*

no obvious effects of mutation, except susceptible to physical shock (temporary paralysis)

Influence of the Environment on Gene Expression

Physical Environment à can have effect on expression of genes1) Temperature

Ex.: Drosophila shibire mutation à recessive temperature sensitive mutationà affects formation of vesicles that transmit signals

between nerve cells‘Restrictive’ temperature: >29C

-flies all die (even without shock)Sh

Shmonohybrid F2

sh*

sh*

ShSh

Shsh*

Shsh*

sh*sh*

lethal

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Influence of the Environment on Gene Expression

4 à Physical Environment

2) Diet and gene expressionnormal biosynthetic pathway in liver

phenylalanine(AA) tyrosine (AA)(from diet) phenylalanine

hydroxylase (PH)

phenylketonuria condition when

phenylalanine(AA) tyrosine (AA)(from diet)

(ph*ph*)X

phenylpyruvic acid

(PhPh or Phph*)

toxin leading to mental retardation

Influence of the Environment on Gene Expression

4 à Physical Environment• Effect of mutation on ph*ph* infants depends on amount of

phenylalanine in diet

infant diet with AA phenylalanine à toxic effectsinfant diet with low phenylalanine à no effects

same genotype,different phenotype depending on environment

>Therefore, all babies in the United States and Canada are tested for PKU right after birth via blood test via a heel stick.>Positive test result indicates ph*ph* genotype, and diet low in phenylalanine is prescribed

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Influence of the Environment on Gene Expression

4 à Genetic Environment or ‘Background’ can influence gene expression

à ploidy level à genderà different species

Ex.: Pattern baldness à gender influenced traità manifested as receding hairline

• males (homozygotes and heterozygotes affected)– à b*b* and Bb*– à prematurely bald

• females (only homozygotes affected)– à b*b* only– à thinning of hair

• Mutant allele sensitive to amount of testosterone which is higher in males

Expression different depending on sex of individual

1. PENETRANCE = Frequency of individuals that show the expected phenotype

Complete penetrance: All individuals show expected phenotype

Incomplete penetrance: Some individuals with mutant fail to exhibit the trait

e.g.: expected mutant ‘a*a*’ has wildtype ‘A’ phenotype

Traits may vary in how reliably they are expressed:

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Incomplete Penetrance Example: Polydactyly

4With incomplete penetrance, individuals do not express the trait even though they must have allele (Pp+)

è Dominant mutation that leads to extra digit (P)è Individuals with only one copy (PP, Pp+)will show trait

must have alleleeven though wildtype in phenotype

Pp+ p+p+

Pp+ p+p+

Pp+Pp+Pp+p+p+

Pp+

2. Expressivity = Variation in expression of trait

Low expressivity: Individuals clearly fall into genetic categories

High expressivity: High level of expression of trait

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Variable ExpressivityExample: the Lobe Eye Dominant Mutation

4A trait is not manifested uniformly among individuals that show it.

4LL = Lobe Eye4Ll+ = Lobe Eye4 l+l+ = wildtype round eye

All flies have same genotype (Ll+), but expression is variable

Near wildtype individuals might be mis-categorized in an experiment

Pigment intensity

>all individuals genetically the same>all ‘should’ show same phenotype

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All ‘Extensions’ so far have to do with variation or interactions having to do with single genes

One must also consider:1) Interactions among multiple gene loci:

è Epistasis

2) Ability of one gene to affect multiple traitsè Pleiotropy

Epistasis = gene interactions4In epistasis, an allele of one gene overrides

(or masks) the effect of another gene on the phenotype.

4Epistasis occurs because of how genes relate to one another in a molecular pathway

Epistasis Models (among many!)1. End-Transporter Epistasis2. Linear Pathway Epistasis

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Epistasis

4Model 1: End-Transporter Epistasis

4In Drosophila,– The cinnabar mutation (cn) produces bright red eyes.– The white (w) mutation produces white eyes.– When both mutations are present in the same fly, the

eyes are white.– The white mutation is epistatic to (overrides) the

cinnabar mutation.

Pathway that explains epistasis in Drosophila eye color:

w+pigment eyes (dark red)

(transporter)

brown pigmentsynthesis (cn+)

red pigmentsynthesis (b+)

if ww à no transport, eyes are whiteif cn cnà no brown pigment, eyes are red (cinnabar)

Both: cn+___ ww = white eyescncn ww = white eyes

w overrides cn(w is epistatic to cn)

“End-Transporter” Epistasis

brown&

red

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dihybrid cross: cn+cn w+w x cn+cn w+w

cn+w+ cn+w cnw+ cnw

cn+w+

cn+w

cnw+

cnw

+ + + + + + + +

+ +

+ +

+ +

+ +

+ +

__ ww __ ww

__ ww __ ww

white white

white white

cncnw+_ cncnw+_

cncnw+_

cinnabarcinnabar

cinnabar

9:4:3 ratio

2. “Linear Pathway” EpistasisEpistatic Control of Flower Color in Sweet Peas

each mutant overides the wildtype allele of the second gene

must have at least one C and one P to produce purple pigment; otherwise white

9:7 ratio results

(purple)(white)(white)(white)

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Pleiotropy = ‘one gene, many traits’

4 A single gene that affects many aspects of the phenotype is “pleiotropic”

4 Ex1: Mutations in the PH gene (ph*)cause:

– mental impairment (PKU)– light hair color– presence of metabolites in

blood and urine

4 Ex2: Mutations in the Drosophila singed gene affect bristle shape and also egg production.

EPISTASIS PROBLEM 1

Summer squash plants with the dominant allele Cbear white fruit, whereas plants homozygous for the recessive allele c bear colored fruit. When the fruit is colored, the dominant allele G causes it to be yellow; in the absence of this allele (that is with the genotype gg) the fruit color is green. Assume that C and G genes assort independently.

What are the F2 phenotypes and proportions expected from intercrossing the progeny of CC GGand cc gg plants?

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EPISTASIS PROBLEM 2

Fruit flies homozygous for the recessive mutation scarlet have bright red eyes because they cannot synthesize brown pigment. Fruit flies homozygous for the recessive mutation brown have brownish-purple eyes because they cannot synthesize red pigment. Fruit flies homozygous for both of these mutations have white eyes because they cannot synthesize either type of pigment. The brown and scarletmutations assort independently.

If fruit flies that are heterozygous for both of these mutations are intercrossed, what kinds of progeny will they produce, and in what proportions?