Download Pedigree Analysis and Hardy- Weinberg Positive Family

Pedigree Analysis and HardyWeinberg
Positive Family History
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First degree relatives
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First / second degree relatives
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Monogenic conditions
Complex disorder
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Diabetes, cancer
“Red Flags” in a Family History
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Number of relatives affected
Degree of relationship to proband
Age of onset
Least affected sex
Related disorders
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Practicum Question I
Inheritance pattern?
Practicum Question II
Albinism in humans is controlled by a recessive
gene (c).From a marriage between a normally
pigmented carrier father and a mother with
albinism, what proportion of children would
be expected to be affected with albinism?
a. Draw a punnett square
b. What is the chance any pregnancy would
result in a child affected with albinism?
A.
Draw a punnett square.
B. What is the chance any pregnancy would result in a
child affected with albinism?
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Practicum Question III
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III. Don and his maternal grandfather, Barry, both have hemophilia A.
Don's wife, Diane, is his maternal aunt's daughter. Don and Diane have
one son, Edward, and 2 daughters, Elise and Emily, all of whom have
hemophilia A. They also have an unaffected daughter, Enid. Hemophilia
A is X-linked recessive.
a. Draw the pedigree.
b. Why are Elise and Emily affected?
c. What is the probability that a son of Elise would be hemophilic?
What is the probability that her daughter would be hemophilic? (Her
husband does not have hemophilia A ?
d. If Enid's husband does not have hemophilia A, what is the
probability that a son would have hemophilia? A daughter?
Practicum Question IV
Cathy is pregnant for the third time. Her first child, Donald, has CF, her second
child, Susan, does not. Cathy has two brothers, Charles and Colin, and a sister,
Cindy. Charles is married to an unrelated woman, Ann, and has a two year old
daughter, Debbie. Cathy's parents are Bob and Betty. Betty's sister, Barbara, is
the mother of Cathy's husband, Calvin. There is no previous history of CF (Cystic
Fibrosis).
a. Sketch the pedigree.
b. What is the pattern of transmission of CF and what is the risk of CF in the
child of this pregnancy?
c. How does the risk of CF in Donald's first cousin, Debbie, compare with the
general population risk of 1/2000?
d. Which people in the pedigree are obligate heterozygotes?
e. What is the chance that Susan is a CF carrier?
Hardy – Weinberg Law
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Calculation of allele frequencies in a
population
The relative frequencies of
heterozygotes and homozygotes are
mathematically related to allele
frequencies
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Hardy – Weinberg Law
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Assumptions
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Randomly mating population
Allele frequencies will remain constant from
generation to generation provided none is
under selection pressure (+ or -)
Large population size
Absence of gene flow (drift)
Hardy – Weinberg Law
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Diallelic System
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Frequency of dominant allele (A) = p
Frequency of recessive allele (a) = q
(p + q)2 = 1
Frequencies of genotypes
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AA = p2
Aa = 2pq
aa = q2
Hardy Weinberg Law
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Example:
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Phenylketonuria occurs in US whites at a
frequency of ~1/15,000. What is the
frequency of carriers in the US white
population?
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Sample pedigree 1
I
1
2
3
1
2
3
1
2
4
II
4
5
III
Sample pedigree 2
I
II
1
2
1
3
2
III
3
4
1
2
4
5
6
Sample pedigree 3
I
II
III
1
2
1
2
3
1
2
3
4
5
3
4
4
6
7
5
Sample pedigree 4
5
6
11
2
7
8
I
3
9
10
13
14
II
1
4
12
III
Sample pedigree 5
I
II
III
1
1
2
1
2
2
3
3
4
5
3
6
4
4
7
8
5
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