MCD – Genetics 8 - Population genetics
Anil Chopra
1.
Describe allele frequencies in a population based on the Hardy-Weinberg
Equilibrium.
A population is a LARGE number of people whose genes are sampled to make the next generation (random mating, outbreeding).
The ‘gene pool’ is the range of genes available to determine the genotype of the next generation.
Recombination is what makes us different to our siblings and from each other
(unrelated). This is good for the species -allows organisms to develop and retain diversity. It also allows us to track genes and/or chromosomes in families and in populations (polymorphisms).
Polymorphism is defined as the occurrence in a population of two or more genetically determined forms (alleles) in frequencies whereby the rarest could not be maintained by mutation alone . Convention says that polymorphic alleles will be greater than 1% in frequency. Can be at protein or DNA level – not disease-causing themselves.
The Hardy-Weinberg law states that allele frequencies and genotype frequencies are constant from generation to generation in a population that is :-
– large and randomly mating
– with no selection, mutation or migration
Dominant traits do not increase at the expense of recessive traits. This is because, the offspring of two heterozygous parents will have ¾ chance of receiving the dominant phenotype and ¼ chance of receiving the recessive phenotype.
Hardy Weinberg equations
If a gene has 2 alleles A and a, and the alleles have frequencies of p and q , then p + q = 100% or 1.
2pq = carrier frequency for a recessive disease q2 = frequency of homozygotes for a recessive disease
2.
Explain how selection and consanguinity affect disease occurrence
3.
Explain founder and migration effects in a population
4.
Explain population isolation and assortative mating
If the carrier frequencies in a population do not change, the population is said to be in Hardy Weinberg equilibrium. This however can change if there is:
Selection: when an allele increases reproductive fitness, it is likely to increase in frequency and when an allele decreases reproductive fitness, it is likely to decrease in frequency.

Mutation: if a particular locus shows a high mutation rate (or a generation is exposed to excess of mutagens e.g. radiation), it will lead to an increase in proportion of mutant alleles in the population.
Migration: alleles introduced into the population by migration and subsequent intermarriage will change allele frequencies. Slow diffusion of alleles across a racial or geographic boundary is known as gene flow .
Population isolation: refers to populations or subgroups which are (more or less) separated reproductively by geography or culture. A mutated allele might be transferred down to a large number of offspring.
Assortative mating: tendency for humans to choose partners who share characteristics such as height, intelligence and racial origin.
Consanguinity: this is the term for marriage between blood relatives (at least one common ancestor no more remote than a great-great-grandparent, i.e. they share more than 1/32 genes) Recessive traits are more frequent in the offspring of consanguineous mating.
Founder effects: occurs when a small group of people, which include carriers of a genetic disorder, create a new population, so that either the carrier status is disproportionate, e.g., rare disorders which occur at high frequency.
5.
Using two examples explain the basis of heterozygous advantage
Heterozygous Advantage : e.g. Sickle cell anaemia. Those that are homozygous for sickle cell anaemia are immune to malaria because if red blood cells are infected they undergo sickling and are rapidly destroyed. e.g. Cystic fibrosis. Since the disease is either lethal before reproductive age and males are sterile you might expect the disease to die out. This is not the case. We do not know what the advantage is for CF carriers, but perhaps it was resistance to a previously endemic diarrhoeal disease.
6.
Calculate the carrier frequency for a recessive disease.
Cystic fibrosis affects 1 in 2000 children born in populations of North European origin. What is the carrier frequency for this recessive disease?
How many carriers in 350 Caucasian people?
We know that p+q = 1, carrier frequency = 2pq, q2 is frequency of recessive disease:
1/2000 = q2, therefore q = 0.022 p = 1-q, therefore p = 1 - 0.022 = 0.978
2pq = 2 x 0.978 x 0.022 = 0.043 or 1/23 is the carrier frequency.
0.043 x 350 = 15 carriers in 350 Caucasians.

7.
Calculate the risk of having an affected child in a family where a relative has a known disease
A healthy female patient (*) has a brother with phenyl- ketonuria (PKU). She wants to marry her maternal first cousin and comes to you for advice on whether any children of theirs will have PKU.
Female patient has 2/3 chance of being a carrier of p allele from her brother. Cousin has
1/4 chance of inheriting p allele from family.
However, he also has the population chance of being a carrier (incidence is 1:10,000, so calculate
2pq).