Past exam of the mathematics course of the University of Cambridge / 2003 / iii / Paper 40 / 5 / i / Solution

Genetic linkage analysis asks whether a genetic marker and a disease genetic locus cosegregate within families more often than would be expected under independent assortment. It uses pedigrees and Mendelian segregation to estimate the recombination fraction $\theta$, with evidence for linkage arising when the data favor $\theta <1/2$. Even when founders are in linkage equilibrium, linked loci can show familial cosegregation.

Genetic association analysis instead asks whether observed allele or genotype frequencies differ with disease status in a sampled population, often comparing cases with controls. It can detect a causal variant or a correlated genetic marker through linkage disequilibrium; population structure and selection can also create association. Linkage is about familial transmission; association is about population dependence. Neither an association alone nor a low family recombination estimate establishes that the marker itself causes disease.