Medical and Molecular Genetics
Lecture 9 Population Genetics I and II
1) Define the following terms: population genetics, epidemiology, genetic
epidemiology, random mating, assortative mating, consanguinity, coefficient of
inbreeding, heterozygote advantage, and founder effect.
Population genetics – the study of the distribution of genes in a population and of
how the frequencies of genes and genotypes are maintained or changed.
Epidemiology – the study of the interrelationships of genetic and environmental
factors that determine the frequency and distribution of diseases in human
populations.
Genetic epidemiology – can be viewed as a fusion of population genetics and
epidemiology, focusing on the inherited causes of disease in populations.
Random mating – mating takes place at random with respect to genotypes in pop.
Assortive mating – choosing a mate based on a particular trait.
Consanguinity – mating of related individuals
Coefficient of inbreeding (F) – the probability that a homozygote has received both
alleles of a pair from an identical ancestral source.
Heterozygote advantage – heterozygotes have a higher reproductive fitness relative to
either type of homozygote.
Founder effect – a high frequency of a mutant gene in a population founded by a
small ancestral group.
2) Calculate the frequency of the alleles for a gene (in a two-allele system) given the
number of individuals in a population with various phenotypes and genotypes.
Genotype
AA Aa aa
Frequency
p2 2pq q2 and p2 + 2pq + q2 = 1
3) Define a population in Hardy-Weinberg equilibrium. A population where
genotypes are distributed in proportion to the frequencies of individual alleles and
remain constant from generation to generation. It must have the following
characteristics: 1) random mating, 2) a constant mutation rate, 3) no selection, 4) no
random fluctuation or genetic drift (sufficiently large), 5) no migration or gene flow.
4) Apply the Hardy-Weinberg principle to calculate the frequency of a common
recessive gene in a population.
First, take the frequency (ex. 1/2000) as the aa genotype = q2 = 1/2000 or q = 0.022
Second, the normal allele can be extrapolated: p = q – 1 therefore p = 0.978
Third, find the number of heterozygotes Aa: 2pq = 2(0.978)(0.022) = 0.044
Finally, the frequency of homozygous recessive and heterozygotes = 0.05% and 4.4%
5) Apply the Hardy-Weinberg principle to calculate the frequency of a rare
recessive gene in a population.
First, take the frequency (ex. 1/10,000) as the aa genotype = q2 = 1/10,000 or q = 0.01
Second, find p = 1 – q, which is approximately equal to 1
Third, find the number of heterozygotes where 2pq ~ 2q
So, the number of heterozygous carrier (2pq) greatly exceeds homozygous recessives
6) Apply the Hardy-Weinberg principle to calculate the frequency of a common xlinked gene in a population.
First, take the affected male population 8% q = 0.08
Second, find the male frequency (ex. Color blindness) X+ p = 0.92 and Xcb q = 0.08
Third, find the female frequency X+/X+ p2 = 0.846, X+/Xcb 2pq = 0.147, and
Xcb/Xcb q2 = 0.0064.
So, total frequency male 8% female 0.64%.
7) Calculate the coefficient of inbreeding (F) for a first cousin mating.
First, determine the ‘loops’ of consanguinity, one loop for each ancestor in common.
The loop is a continuous path through a common ancestor, starting with one
parent and ending with the other, not including the proband (n = number of
ancestors in the loop).
Second, the inbreeding coefficient is calculated by using the equation: F = Σ(1/2)n
So, if loop 1 has 5 ancestors and loop 2 has 5 ancestors then F = (1/2)5 + (1/2)5 = 1/16
8) Discuss the relationship between fitness (f) and the coefficient of selection (s).
Biological fitness is a way of taking into account both survival to reproduction and
reproduction itself to evaluate genotypes relative to one another with respect to
transmitting genes to the next generation. Selection is complimentary to the fitness
value (selection coefficient = s = 1 – f), and measures the intensity of selection
against a genotype.
9) Discuss the mechanisms of maintenance of a balanced polymorphism within a
defined population. Balanced polymorphisms are maintained through selective
advantage of the heterozygote over either of the homozygotes. Any change in
selective pressures would be expected to lead to a change in the relative frequency of
the allele.
10) Compare and contrast genetic drift and gene flow. Genetic drift is the random
fluctuation of gene frequencies in a small population, where gene frequencies are
unbalanced because the sampling was too small (founder effect). Gene flow is the
slow diffusion of genes across a population barrier where a migrant population’s
genes are slowly integrated into the gene pool.
11) Calculate the mutation rate for an autosomal dominant disorder, given the
coefficient of selection and the frequency of the mutant allele in a population.
Mutation rate (µ) for autosomal dominant genes may be calculated as follows:
µ = s x q (µ = mutation rate; s = coefficient of selection, which is calculated as
s = 1 – f; and q = mutant allele frequency).