Lecture 3-More deviations from Mendelian ratios

Lecture 3-More deviations from Mendelian ratios

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Print your name, TA name, and section # at top of card and place in the appropriate box at the front of the room.

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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 XAXa XAYAdults

Gametes XA XA Y

XA

YXA

Xa

Xa

XAXA

XAXa XaY

XAYFemale

Male

HeterogameticSex

Sex Linkage: birds, butterflies

Diploid ZBW ZBZb

Adults Female Male

Gametes ZB ZB Zb

ZB

ZbZB

W

W

ZBZb

ZBW ZbW

ZBZb

Female

Male

HeterogameticSex

HomogameticSex

Y-linked inheritance

Hairy ears

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.



Male pattern baldness: what kind of inheritance?

Sex influenced phenotype

Genotype Female Malebb Bald Baldbb’ Not bald Baldb’b’ Not bald Not 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: phenylketonuriaGenetic 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 diseaseFragile-X syndromeKennedy diseaseMyotonic muscular

dystrophy

Fragile X syndromeSymptoms: 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”: 60-200 repeatsFull Mutation: > 230-1000s. 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 DiseaseAutosomal dominant lethal (chromosome 4)Progressive neurological deteriorationFirst symptoms appear after reproductive ageOne 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 ggF1: Gg X GgF2: 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 WWF1: Gg Ww X Gg WwF2: 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 RuleThe 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 1Retinitis 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

SolutionP: 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 2In 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 dominanceEpistasis

Expected F2 ratio?1:2:1Variation on 9:3:3:1

Genetic Model

P: SphericalGen: AAbb

x Spherical aaBB

F1: AllAa

DiskBb

F2: 35 diskRatio: 9

25 Spherical6

4 long1

Gen: A-B- aaB- or A-bb aabb

Sex LinkageQ: 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

EpistasisLethal allelesX and Y linkageSex Influenced InheritanceTemperature or nutrition sensitive allelesGenetic anticipation

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Lecture 3-More deviations from Mendelian ratios