For a recessive disease whose gene has been localized on the human gene map, a new method is described for estimating the population frequency of the disease allele. The method focuses on affected individuals whose parents are First cousins, where parents and grandparents are genotyped for highly polymorphic markers at the disease gene. The primary statistic is the proportion of such probands who are autozygous (homozygous due to identity by descent of the two disease alleles), where this 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 affected individuals whose parents are First cousins; this proportion is also a function of the disease allele frequency. For small to moderate sample 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.

Keywords:
Dahlberg method, Allele frequency, Recessive disease
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1997
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