MARKER SELECTION FOR THE TRANSMISSION DISEQUILIBRIUM TEST, IN RECENTLY ADMIXED POPULATIONS/

Recent admixture between genetically differentiated populations can re sult in high levels of association between alleles at loci that are le ss than or equal to 10 cM apart. The transmission/disequilibrium test (TDT) proposed by Spielman et al. (1993) can be a powerful test of lin kage between disease and marker loci in the presence of association an d therefore could be a useful test of linkage in admired populations. The degree of association between alleles at two loci depends on the d ifferences in allele frequencies, at the two loci, in the founding pop ulations; therefore, the choice of marker is important. For a multiall elic marker, one strategy that may improve the power of the TDT is to group marker alleles within a locus, on the basis of information about the founding populations and the admired population, thereby collapsi ng the marker into one with fewer alleles. We ha cie examined the cons equences of collapsing a microsatellite into a two-allele marker, when two founding populations are assumed for the admired population, and have found that if there is random mating in the admired population, t hen typically there is a collapsing for which the power of the TDT is greater than that for the original microsatellite marker. A method is presented for finding the optimal collapsing that has minimal dependen ce on the disease and that uses estimates either of marker allele freq uencies in the two founding populations or of marker allele frequencie s in the current, admired population and in one of the founding popula tions. Furthermore, this optimal collapsing is not always the collapsi ng with the largest difference in allele frequencies in the founding p opulations. To demonstrate this strategy, we considered a recent data set, published previously, that provides frequency estimates for 30 mi crosatellites in 13 populations.