Population Genetics

Question 1

What are polymorphisms?

Answer 1

Polymorphisms are variants that occur in a specific population. This allele over generations becomes more and more frequent due to pressures. Going from 1 out of 1000 to 1 out of 100 in a population.

Question 2

What is Hardy Weinberg and its four assumptions.

Answer 2

1. Random mating
2. No changes in population due to large migration
3. No large fluctuation in allele frequency by natural selection/ genetic drift, bottleneck inbreeding
4. No positive or negative selection: all produce equally well

p^2 + 2pq + q^2 = 1
p+q= 1
The total frequency of an allele p is
p^2 + 2p

Frequency of being a carrier/heterozygous (2pq)

Question 3

What are five things that lead to genetic variations?

Answer 3

1. Natural selection: selection against homozygous individuals and favoring heterozygotes.
2. Genetic drift: in small populations, by chance a disproportional distribution from one generation to the next
3. Founder effect: 1 ancestor’s arrival in the gene pool introduces a rare deleterious allele
4. Bottleneck effect: high frequency of an allele in a population that underwent tight population constrictions.
5. Inbreeding increases the amount of homozygotes.

Question 4

A mother is a known carrier. The father is screened with a test that came negative. Carrier frequency is 1:25 and detection is 90%. Calculate the chance that the offspring has CF.

Answer 4

1/25 x 1/10 x 1/4 = 1 in 1000 chance.

1/10 corresponds to the chance that the test gave a false positive.

Question 5

Varied penetrance:

Huntington disorder. The great grandmother is a carrier. The grandfather is asymptomatic (age 60) and the father is asymptomatic (age 35) 
at 60 (there is a 20% of being asymptomatic and still being a carrier) 

at 35 there is a 50% chance.

What is the chance the child will be a carrier?

Answer 5

Father’s chance of being a carrier

(grand father) (1/2)(2/10). Grandmother a known carrier (1/2)

(1/2)(1/2)(2/10) = 1/20

Father’s chance of being a carrier given the condition that he is asymptomatic at 35

(1/20)(.5) = 1/40
And passing mutant allele to the child…

1/40 (1/2) = 1/80

Question 6

Describe Bayesian analysis.

Answer 6

Two subjects, the mother and whether the patient is a carrier taking account the patient’s siblings.

You consider three scenarios.
Mother is a carrier and patient is a carrier.
Mother is a carrier and patient is not a a carrier.
Mother is not a carrier so patient is also not a carrier.

Prior probability - is just the mendelian probability that the mother is a carrier or not. Yada yada, 1/2 for all.

Conditional probability is additional information to take into account. 4 unaffected brothers. (1/2)(1/2)^4. but for non carrier scenario, we assume 100% so (1)(1).

Joint probability is combining prior and conditional (mother and patient)

Then posterior is taking one joint probability divided by all the probabilities. That will give you the probability this scenario is true.

Question 7

How would you know the frequency of an allele given frequency of affected males with an XLR?

Answer 7

The frequency of the mutation would be = to amount of affected males so.

If frequency of affected males is 1/100,
q = 1/100.

Question 8

What is negative assortive mating and its effect?

Answer 8

Negative assortive mating refers to preferentially selecting members that are phenotypically (and likely genetically) different from you (twinkies)

It will increase the amount of heterozygotes and therefore decrease the mutation rate of AR diseases