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Exam II Thursday 28 Feb 2013

Coverage: All material since last exam Lecture 5: Sex-linkage part (incl. XX/XY, ZZ/ZW, etc.) Lecture 6: Linkage (incl. repulsion/coupling) Lecture 7: LOD score analysis Lecture 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 Set 4) Complementation Problem Set >Lod Score (Lab worksheet) >Mode of Inheritance (F1/F2 analysis Lab assignment) >Quizzes: Sex-linkage (Q2); Linkage (Q3)

Chapter 4 Allele 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 However, in some cases Ww or WW might be white

Factors that may affect expression of trait: 1. Physical Environment 2. Genetic Environment 3. Penetrance of trait 4. Expressivity of trait

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Influence of the Environment on Gene Expression

Physical Environment can have effect on expression of genes

1) Temperature
Ex.: Drosophila shibire mutation recessive temperature sensitive mutation affects formation of vesicles that transmit signals between nerve cells Permissive temperature: 25C -flies are viable and fertile
Sh Sh ShSh Shsh* sh* Shsh* sh*sh*

monohybrid F2
sh*

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

Influence of the Environment on Gene Expression

Physical Environment can have effect on expression of genes

1) Temperature
Ex.: Drosophila shibire mutation recessive temperature sensitive mutation affects formation of vesicles that transmit signals between nerve cells Restrictive temperature: >29C -flies all die (even without shock)
Sh Sh ShSh Shsh* sh* Shsh*

monohybrid F2
sh* sh*sh*

lethal

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Influence of the Environment on Gene Expression

4 Physical Environment

2) Diet and gene expression

normal biosynthetic pathway in liver phenylalanine(AA)
(from diet)
(PhPh or Phph*) phenylalanine hydroxylase (PH)

tyrosine (AA)

phenylketonuria condition when phenylalanine(AA)

(from diet)
(ph*ph*)

tyrosine (AA) phenylpyruvic acid

toxin leading to mental retardation

Influence of the Environment on Gene Expression

4 Physical Environment Effect of mutation on ph*ph* infants depends on amount of phenylalanine in diet infant diet with AA phenylalanine toxic effects infant diet with low phenylalanine 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 Genetic Environment or Background can influence gene expression ploidy level gender different species Ex.: Pattern baldness gender influenced trait manifested as receding hairline males (homozygotes and heterozygotes affected) Expression b*b* and Bb* different prematurely bald depending on sex females (only homozygotes affected) of individual b*b* only
thinning of hair

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

Traits may vary in how reliably they are expressed: 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

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Incomplete Penetrance Example: Polydactyly

Dominant mutation that leads to extra digit (P) Individuals with only one copy (PP, Pp+)will show trait 4 With incomplete penetrance, individuals do not express the trait even though they must have allele (Pp+)
Pp+ p+p+

must have allele even though wildtype in phenotype

Pp+

p+p+

p+p+

Pp+

Pp+

Pp+

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 Expressivity Example: the Lobe Eye Dominant Mutation

4 A trait is not manifested uniformly among individuals that show it. 4 LL = Lobe Eye 4 Ll+ = Lobe Eye 4 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: Epistasis 2) Ability of one gene to affect multiple traits Pleiotropy

Epistasis = gene interactions

4In 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 Epistasis 2. 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.

End-Transporter Epistasis Pathway that explains epistasis in Drosophila eye color:

brown pigment synthesis (cn+) red pigment synthesis (b+) brown & red

pigment

eyes (dark red) (transporter)

w+

if ww no transport, eyes are white if cn cn no brown pigment, eyes are red (cinnabar) Both: cn+___ ww = white eyes cncn ww = white eyes w overrides cn (w is epistatic to cn)

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dihybrid cross: cn+cn w+w x cn+cn w+w cn+w+ cn+w+ cn+w ++ ++ cn+w ++ __ ww
white

cnw+ ++

cnw ++ __ ww
white

++
cncnw+_
cinnabar

cnw+

++

++

cncnw+_
cinnabar

cnw

++

__ ww
white

cncnw+_
cinnabar

__ ww
white

9:4:3 ratio

2. Linear Pathway Epistasis Epistatic Control of Flower Color in Sweet Peas

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

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

each mutant overides the wildtype allele of the second gene

9:7 ratio results

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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 C bear 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 GG and 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 scarlet mutations 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?

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