Hardy Weinberg Law

Question 1

What is the Hardy Weinberg equation?

Answer 1

p2 + 2pq + q2 = 1
●For recessive disease 2pq = carrier frequency
oq=minor allele, for most rare diseases p can be assumed to be 1
●For X-linked diseases 2q=females, q is X allele frequency and also male frequency because males have only 1 X
●For dominant conditions, p2 + 2pq is the dominant phenotype frequency

Question 2

Hardy-Weinberg Assumptions

Answer 2

●	Random mating
●	No selection
●	No new mutations
●	Population is infinitely large
●	No migration

Question 3

Violations of HW Assumptions: Random mating

Answer 3

●Assortative mating, Population stratification, Consanguinity
oCoefficient of inbreeding (F) – probability that a person who is homozygous at a particular locus inherited both alleles from a single ancestor
oCoefficient of relationship (R) – measure of the degree of consanguinity between two individuals
▪Ex. First cousin’s generally share 1/8 of their genes, R=1/8
oF= R x (1/2)
oExceptions to random mating INCREASE proportion of homozygotes, DECREASE proportion of heterozygotes

Question 4

Violations of HW Assumptions: No selection

Answer 4

●Fitness (f) – probability of passing on an individual’s genes to the next generation when compared to average probability for the population
●Coefficient of selection (s) – measure of the loss of fitness (s=1-f)

Question 5

Selection against AD mutations

Answer 5

o When f=0 there is complete selection against the allele and almost all affected individuals represent de novo events

o When f=1 there is no selection against the mutant allele and virtually all affected individuals inherited the mutation

o µ (new mutation rate) = q (allele frequency) x s

Question 6

Selection against AR conditions

Answer 6

●Selection against AR conditions does not really occur due to the presence of unaffected carriers with normal fitness

Question 7

Selection against X-linked mutations

Answer 7

oWhen f=1, 1/3 of mutant alleles are in males and 2/3 are in females

oWhen f=0, 1/3 of mutant alleles are lost with each generation

  ▪2/3 prior risk to the mother of an isolated affected male (Think Bayes - Haldane’s law!!!)

●Heterozygote advantage
●Heterozygote disadvantage

Question 8

Violations of HW Assumptions: No new mutations

Answer 8

●µ=q x s

●Use for autosomal dominant conditions, however in recessive conditions parents are obligate carriers

Question 9

Violations of HW Assumptions: Population is infinitely large

Answer 9

●Genetic drift – variation in observed frequencies of alleles due to random sample of the pool of gametes in each generation
oNegligible effect in a large population
oStrong effect in a small population

●Founder effect/Population bottleneck (form of genetic drift) – formation of a genetic isolate
oFounder mutations
oAJ mutations (Bottleneck)

Question 10

Violations of HW Assumptions: No migration

Answer 10

●Gene flow/Population admixture – non-random slow diffusion of a gene across an ethnic or geographical barrier
o Occurs by migration