Likelihood Analysis of Disequilibrium Mapping,
and Related Problems
Bruce Rannala and Montgomery Slatkin
Department of Integrative Biology, University of California Berkeley, Berkeley
American Journal of Human Genetics,
62(2), 459-473 (1998)
Abstract
In this paper a theory is developed that provides the sampling
distribution of alleles at a diallelic marker locus closely linked to a
low-frequency allele that arose as a single mutant. The sampling
distribution provides a basis for maximum-likelihood estimation of either
the recombination rate, the mutation rate, or the age of the allele, provided
that the two other parameters are known. This theory is applied to (1) the
data of Hästbacka et al., to estimate the recombination rate between a
locus associated with diastrophic dysplasia and a linked RFLP marker; (2)
the data of Risch et al., to estimate the age of a presumptive allele causing
idiopathic distortion dystonia in Ashkenazi jews; and (3) the data of
Tishkoff et al., to estimate the date at which, at the CD4 locus,
non-African lineages diverged from African lineages. We conclude that
the extent of linkage disequilibrium can lead to relatively accurate
estimates of recombination and mutation rates and that those estimates
are not very sensitive to parameters, such as the population age, whose
values are not known with certainty. In contrast, we also conclude that, in
many cases, linkage disequilibrium may not lead to useful estimates of
allele age, because of the relatively large degree of uncertainly in those
estimates.
Association Studies