Chapter 7 Population Genetics

Introduction Genes act on individuals and flow through families. The forces that determine gene frequencies act at the level of populations. Study of these forces can have important implications for medicine. Firstly, we can understand why some populations appear to be singled out for particular genetic disorders and may be relatively free of others. Secondly, the principles of population genetics provide tools for calculating gene frequencies to use in genetic counselling.

Introduction The frequency of carriers for recessive traits cannot be determined directly but can be calculated using a simple equation that is the cornerstone of population genetics. Population genetics helps us to understand the significance of genetic variation, and has provided the basis for the intersection of genetics with public health in the form of population screening programs.

Hardy Weinberg Equilibrium The Hardy–Weinberg equilibrium provides the cornerstone for our understanding of population genetics. The concept was established in 1908 independently by the English mathematician G.H. Hardy and the German physician W. Weinberg. Their formulation states a simple relationship between the frequency of alleles at a genetic locus and the genotypes resulting from those alleles.

Hardy Weinberg Equilibrium The Hardy–Weinberg equilibrium depends on a number of assumptions. Mating must be random with respect to genotype. Also, the population is assumed to be very large, so statistical fluctuations will be negligible. There must be no mutation of A alleles into a, or a into A. Finally, individuals of all genotypes must be equally capable of reproduction (i.e., there must be no selection).

How is the Hardy–Weinberg equilibrium used to calculate carrier frequency of a recessive disorder? Consider the recessive condition cystic fibrosis. In this case, the A allele is the wild type and a is the cystic fibrosis mutation. The frequency of aa – that is, of individuals affected with cystic fibrosis – is 1 in 2500 in Northern European whites. Thus q2 = 1/2500, and hence q = 1/50. Because p + q = 1, p must be 49/50. The carrier frequency, then, is 2pq = 2(49/50)(1/50) ≈ 1/25 in this population. Hardy Weinberg Equilibrium

The Hardy–Weinberg equation also predicts that the gene frequencies will remain stable from generation to generation, provided that certain conditions are met. The ideal Hardy–Weinberg population must fulfill several requirements that may not be met in real populations. Deviations From the Hardy Weinberg Equilibrium

Selection

Balanced Polymorphism Deviations From the Hardy Weinberg Equilibrium

Founder effect Genetic bottleneck