The effect of marker characteristics on the power to detect linkage disequilibrium due to single or multiple ancestral mutations

An important design issue in allelic association studies for mapping diseas e genes is the choice of markers. We have used a simple model of a founder population: similar to those of Ott Sr Rabinowitz (1997) and Chapman & Wijs man (1998), to explore the effect of the number of alleles at a marker poly morphism on the power to detect linkage disequilibrium due to single or mul tiple ancestral disease mutations. We show that the optimal number of allel es is more than 2 even in the case of a single ancestral disease mutation, and much higher still if multiple ancestral mutations are present. In large samples: much power is lost by using too few alleles, but relatively littl e power is lost by using too many alleles. These results confirm the desira bility of using highly polymorphic markers or multi-locus haplotypes for as sociation analysis. They also show that multiple ancestral disease mutation s do not necessarily preclude linkage disequilibrium mapping, if highly pol ymorphic markers or multi-locus haplotypes are used.