LD mapping relies instead on the population-wide correlation between two sequence variants. Most variants are single nucleotide polymorphisms (SNPs) (almost always just two alternative nucleic acids at a genomic position). SNP variants that are reasonably common are mutations that occurred thousands of generations ago and then spread, due to chance or natural selection. When a second SNP mutation occurred very close to an earlier one (up to tens of thousands of base pairs [bp] away), then both variant alleles are almost always transmitted to the same children in subsequent generations. Linkage disequilibrium is this non-random association of two alleles. Around 20 years ago, it was proposed that LD could be exploited to “map” or identify disease genes, such as in linkage candidate regions (or in recently isolated populations in which LD spans long distances). (19) If one SNP increases the risk of a common disease, then there will be a statistical association in the population between disease and that SNP (direct association) and several nearby SNPs (indirect association, due to LD).
