Linkage disequilibrium — understanding the evolutionary past and mapping the medical future

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Abstract
Linkage disequilibrium (LD) is the nonrandom association of alleles of different loci. There is no single best statistic that quantifies the extent of LD. Several statistics have been proposed that are useful for different purposes. Recombination interacts in a complex way with selection, mutation and genetic drift to determine levels of LD. As a consequence, local and genome-wide patterns of LD can provide insight into patterns of natural selection and the past history of population growth and dispersal. In humans and other model organisms, LD between marker alleles and traits of interest allow fine-scale gene mapping. Many recent genome-wide association studies have successfully mapped SNPs associated with complex inherited diseases in humans. Unusually high local LD can indicate an allele that has recently increased to high frequency under strong selection. Several methods have been developed to detect selected loci and to estimate the age of alleles using patterns of LD. In humans, the analysis of LD is well underway. The pace is slower in other species, although some model organisms, including mice, dogs, Drosophila and Arabidopsis thaliana, are catching up fast. Extensive analysis of LD in non-model species will be undertaken soon.