1-42 Population Genetics

Question 1

What is the Hardy-Weinberg Law?

Answer 1

p² + 2pq + q² = 1

p² = dominant homozygote frequency, 2pq = heterozygote frequency, q² = recessive homozygote frequency

p + q = 1

p = frequency of allele A, q = frequency of allele a

The H-W Law is most frequently used to determine the carrier frequency from the frequency of individuals born with the disorder.

Question 2

What does the Hardy-Weinberg Law assume?

Answer 2

• The population is large, and matings are random with respect to the locus in question
• Allele frequencies remain constant over time because:
• *a)** There is no appreciable rate of mutation
• *b)** Individuals with all genotypes are equally capable of mating and passing on their genes (i.e., there is no selection against any particular genotype)
• *c)** There has been no significant immigration of individuals from a population with allele frequencies very different from the endogenous population

Question 3

What is Hardy-Weinberg equilibrium?

Answer 3

The conditions under which the H-W Law holds true, allowing us to predict the number of asymptomatic, heterozygous carriers from the frequency of recessive, affected homozygotes.

Question 4

For X-linked recessive traits, how can the male birth rate be used to derive female carrier frequency?

Answer 4

Instead of using q² to denote the frequency of affected individuals, since males only need one copy of an X-linked allele to be affected, use q.

Question 5

What is selection?

Answer 5

Natural selection (s) is the operation of forces that determine the relative fitness of a genotype in the population; fitness (f) is the probability of transmitting genes to the next generation and of the survival in that generation to be passed on to the next.

s = coefficient of selection
f = genetic fitness (1 - s)

For some traits (e.g., sickle cell disease, thalassemia), though a recessive genotype may yield large disadvantages, the corresponding heterozygous genotype may confer an advantage, so there is less selection against these traits.

Question 6

What is the rate for new mutations?

Answer 6

μ = 10^-7 to 10^-8 per locus per generation for SNPs

For rare autosomal dominants: μ = n/2N
n = # affected patients born to unaffected parents, N = total # births

De novo mutations are more likely to be inherited paternally.

Question 7

Why might autosomal recessive disorders achieve high frequencies?

Answer 7

• Founder effect and drift
• Heterozygous advantage (e.g., sickle cell trait)
• Pleiotropy (advantage vs. disadvantage)
• Elevated mutation rate (e.g., very large genes)
• Reproductive compensation (more carriers)
• Multiple loci conferring the same phenotype (locus heterogeneity)
• Hitch-hiking (disadvantageous trait rides along with an advantageous one nearby)
• Genome instability (e.g., dynamic mutations)
• Late onset (post-reproduction)