Sterling Sawaya, Matt Jones, Matt Keller
Some diseases are caused by genetic loci with a high rate of change, and heritability in complex traits is likely to be partially caused by variation at these loci. These hypermutable elements, such as tandem repeats, change at rates that are orders of magnitude higher than the rates at which most single nucleotides mutate. However, single nucleotide polymorphisms, or SNPs, are currently the primary focus of genetic studies of human disease. Here we quantify the degree to which SNPs are correlated with hypermutable loci, examining a range of mutation rates that correspond to mutation rates at tandem repeat loci. We use established population genetics theory to relate mutation rates to recombination rates and compare the theoretical predictions to simulations. Both simulations and theory agree that, at the highest mutation rates, almost all correlation is lost between a hypermutable locus and surrounding SNPs. The theoretical predictions break down for middle to low mutation rates, differing widely from the simulated results. The simulation results suggest that some correlation remains between SNPs and hypermutable loci when mutation rates are on the lower end of the mutation spectrum. Consequently, in some cases SNPs can tag variation caused by tandem repeat loci. We also examine the linkage between SNPs and other SNPs and uncover ways in which the linkage disequilibrium of rare SNPs differs from that of hypermutable loci.