ASCERTAINMENT BIAS IN ESTIMATES OF AVERAGE HETEROZYGOSITY

Population geneticists work with a nonrandom sample of the human genom e. Conventional practice ensures that unusually variable Loci are most likely to be discovered and thus included in the sample of loci. Cons equently, estimates of average heterozygosity are biased upward. In wh at follows we describe a model of this bias. When the mutation rate va ries among loci, bias is increased. This effect is only moderate, howe ver, so that a model of invariant mutation rates provides a reasonable approximation. Bias is pronounced when estimated heterozygosity is < similar to 35%. Consequently, it probably affects estimates from class ical. polymorphisms as well as from restriction-site polymorphisms. Es timates from short-tandem-repeat polymorphisms have negligible bias, b ecause of their high heterozygosity. Bias should vary not only among c ategories of polymorphism but also among populations. It should be lar gest in European populations, since these are the populations in which most polymorphisms were discovered. As this argument predicts, Europe an estimates exceed those of Africa and Asia at systems with large bia s. The magnitude of this European excess is consistent with the versio n of our model in which mutation rates vary across loci.