Transcript Gen_Week1b

Lecture 3-More deviations from
Mendelian ratios
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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
XAXa
Diploid
Adults
Gametes
Heterogametic
Sex
Xa
XA
XA
Y
XA
XAXA
XAY
Xa
XAXa
XaY
XA
Male
Female
XAY
Y
Sex Linkage: birds, butterflies
ZBW
Female
Diploid
Adults
Gametes
Homogametic
Sex
Heterogametic
Sex
ZBZb
Male
W
ZB
ZB
Zb
ZB
ZBZb
ZBZb
W
ZBW
ZbW
ZB
Male
Female
Zb
Y-linked inheritance
Hairy ears
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Male pattern
baldness: what kind
of inheritance?
Sex influenced phenotype
Genotype
bb
bb’
b’b’
Female
Bald
Not bald
Not bald
Male
Bald
Bald
Not bald
Environment-dependent
dependent expression of a
genotype
Siamese or “Himalayan”
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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
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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”: 60-200 repeats
Full Mutation: > 230-1000s. DNA
becomes abnormally methylated,
promoter is inactivated, and gene
silenced.
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Pre-mutation is unstable: maternallyinherited 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)
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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?
Q1: What are the genotypes of the afflicted man’s parents?
A: A- rr
Aa rr
Q1: What is the afflicted man’s genotype?
A: aa rr
Q1: Draw the cross between the afflicted man and his wife.
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
F1:
F2: 35 disk
Ratio: 9
Gen: A-B-
x
All Disk
Aa Bb
25 Spherical
6
aaB- or A-bb
Spherical
aaBB
4 long
1
aabb
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 purebreeding 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