ESTIMATING RECESSIVE DISEASE ALLELE FREQUENCY BASED ON GENETIC MAPS

For a recessive disease whose gene has been localized on the human gen e map, a new method is described for estimating the population frequen cy of the disease allele. The method focuses on affected individuals w hose parents are first cousins, where parents and grandparents are gen otyped for highly polymorphic markers at the disease gene. The primary statistic is the proportion of such probands who are autozygous (homo zygous due to identity by descent of the two disease alleles), where t his proportion is a function of the disease allele frequency. Our map- based method is compared to Dahlberg's method of estimating recessive disease allele frequencies, which is based on the proportion of affect ed individuals whose parents are first cousins; this proportion is als o a function of the disease allele frequency. For small to moderate sa mple sizes and traits that are not too common, our new method is more efficient (for some parameter values dramatically more efficient) than Dahlberg's method.