Lecture 3-More deviations from Mendelian ratios For extra credit question, please use the index cards provided at the back of the room Print your name, TA name, and section # at top of card and place in the appropriate box at the front of the room. Thanks! Extra-credit question: In some cases, not all individuals with a particular genotype show the expected phenotype. The frequency with which a genotype gives rise to the expected phenotype is called the _______________ of that genotype.

Sex Linkage: mammals, flies Diploid X A X a X A Y Adults Gametes XAXA XAXA Y XAXA Y XAXA XaXa XaXa XAXAXAXA XAXaXAXa XaYXaY XAYXAY Female Male Heterogametic Sex

Sex Linkage: birds, butterflies Diploid Z B W Z B Z b Adults Female Male Gametes ZBZB ZBZB ZbZb ZBZB ZbZb ZBZB WW ZBZbZBZb ZBWZBWZbWZbW ZBZbZBZb Female Male Heterogametic Sex Homogametic Sex

Y-linked inheritance

Hairy ears

Male pattern baldness: what kind of inheritance?

Sex influenced phenotype Genotype FemaleMale bbBaldBald bb’Not baldBald b’b’Not baldNot bald

Environment-dependent dependent expression of a genotype

Siamese or “Himalayan” Different allele of the C locus that causes albinism. Temperature sensitive.

Phenotypes are not always a direct reflection of genotypes Temperature-sensitive alleles: Siamese color pattern Nutritional effects: phenylketonuria Genetic anticipation: several genetic diseases

Phenylketonuria Nutritional defect: can’t metabolize phenylalanine. Can lead to severe physical and mental disorders in children, but only if they consume phenylalanine. Disease phenotype can be avoided by eliminating phenylalanine from the diet

Genetic Anticipation Huntington disease Fragile-X syndrome Kennedy disease Myotonic muscular dystrophy

Fragile X syndrome Symptoms: delayed development & mental retardation. More severe in males than females Caused by expansion of triplet repeat (CGG) in a gene on the long arm of the X chromosome Named for breakage of X chromosome in cell preparations.

Fragile X Normal range: 7-52 (average=30) “Pre-mutation”: repeats Full Mutation: > s. DNA becomes abnormally methylated, promoter is inactivated, and gene silenced. Pre-mutation is unstable: maternally- inherited premutation with >100 repeats almost always expands to a full mutation

Genetic Anticipation: Fragile X Most common kind of inherited mental retardation. Named for “fragile site” Due to expansion of 3-base pair repeat (CGG) in a gene near the tip of the long arm of X chromosome.

Fragile X Pre-mutation is unstable: maternally-inherited premutation with >100 repeats almost always expands to a full mutation

Genetic Anticipation causes subsequent generations in a family to be more severely affected by a disease. It does this by increasing the number of triplet repeats in the fragile area of the X chromosome through the generations.

Huntington Disease Autosomal dominant lethal (chromosome 4) Progressive neurological deterioration First symptoms appear after reproductive age One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats All show inverse correlation with age of onset and number of repeats.

Huntington Disease Autosomal dominant lethal (chromosome 4) Progressive neurological deterioration First symptoms appear after reproductive age One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats All show inverse correlation with age of onset and number of repeats.

Huntington Disease Autosomal dominant lethal (chromosome 4) Progressive neurological deterioration First symptoms appear after reproductive age One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats All show inverse correlation with age of onset and number of repeats.

Which is the pedigree of autosomal dominant (like HD)

Genetic Data Analysis I Some simple rules of probability

Sum Rule The combined probability of two events that are mutually exclusive is the sum of the individual probabilities. Clue: look for “or” Q: What’s the probability of rolling a ‘five’ or a ‘six’ on one six-sided die? A: 1/6 + 1/6 = 1/3

Genetic Example: Monohybrid Cross P: GG X gg F1:Gg X Gg F2: 1/4 GG: 1/2 Gg: 1/4 gg What is the probability that the F2 offspring has the dominant phenotype (is either GG or Gg)? 1/4 GG + 1/2 Gg = 3/4 G-

Genetic Example 2: Dihybrid Cross P: GG ww X gg WW F1: Gg Ww X Gg Ww F2: 9/16 G-W- 3/16 G-ww 3/16 ggW- 1/16 ggww Q: What is the probability that an F2 offspring will have the dominant phenotype (G-ww or ggW-) for only one of the two traits? 3/16 G-ww + 3/16 ggW- = 6/16=3/8

Product Rule The probability of several independent events is the product of the individual probabilities. Two events are independent if the occurrence of the first event has no effect on the probability of the second event. Clue: look for “and”. Q: You roll two dice. What’s the probability of getting a ‘two’ on the first one and a ‘five’ on the second one. A: 1/6 * 1/6 = 1/36

Genetic example of product rule P: AA bb CC DD ee ff x aa BB cc dd EE FF F1: Aa Bb Cc Dd Ee Ff x Aa Bb Cc Dd Ee Ff Q: What proportion of F2 progeny will be AA bb Cc DD ee Ff ? A: 1/4 * 1/4 * 1/2 * 1/4 * 1/4 * 1/2 = 1/1024

Epistasis Problem 1 Retinitis pigmentosa, a form of blindness in man may be caused either by a dominant autosomal gene, R, or a recessive autosomal gene, a. Thus only A-rr individuals are normal. An afflicted man whose parents are both normal marries a woman of genotype AaRr. What proportion of the children are expected to suffer from this affliction if R and A are inherited independently? A: A- rr Q1: What are the genotypes of the afflicted man’s parents? A: Q1: What is the afflicted man’s genotype? Q1: Draw the cross between the afflicted man and his wife. Aa rr aa rr

Solution P: Aa Rr x aa rr F1: 1/4 Aa Rr: 1/4 Aa rr: 1/4 aa Rr: 1/4 aa rr A: 3/4 offspring will have the disorder

Epistasis Problem 2 In the summer squash (Cucurbita pepo) spherical fruit is recessive to disk, True-breeding spherical types from different geographic regions were crossed. The F1's were disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results. Q: What’s the first step? A: Notice novel phenotypes: disk, long. Q: What’s the next step? A: Notice there are three F2 phenotypes. What kind of inheritance will give three F2 phenotypes? Incomplete dominance Epistasis Expected F2 ratio? 1:2:1 Variation on 9:3:3:1

Genetic Model P: Spherical Gen: AAbb xSpherical aaBB F1:All Aa Disk Bb F2: 35 disk Ratio: 9 25Spherical 6 4 long 1 Gen: A-B-aaB-or A-bbaabb

Sex Linkage Q: Cinnamon is a sex-linked recessive plumage color in chickens. A cinnamon rooster is crossed to a wild-type hen from a pure- breeding stock. What types of male and female offspring will result from this cross? Q: What’s the first step?

Last class-deviations from Mendelism Epistasis Lethal alleles X and Y linkage Sex Influenced Inheritance Temperature or nutrition sensitive alleles Genetic anticipation