Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci

A multimarker linkage disequilibrium mapping method was developed for the f ine mapping of quantitative trait loci (QTL) using a dense marker map. The method compares the expected covariances between haplotype effects given a postulated QTL position tu the covariances that are found in the data. The expected covariances between the haplotype effects are proportional to the probability that the QTL position is identical by descent (IBD) given the m arker haplotype information, which is calculated using the genedropping met hod. Simulation results showed that a QTL was correctly positioned within a region of 3, 1.5, or 0.75 cM in 70, 62, and 68%, respectively, of the repl icates using markers spaced at intervals of 1, 0.5, and 0.25 cM, respective ly. These results were rather insensitive to the number of generations sinc e the QTL occurred and to the effective population size, except that 10 gen erations yielded rather poor estimates of the QTL position. The position es timates of this multimarker disequilibrium mapping method were more accurat e than those from a single marker transmission disequilibrium test. A gener al approach for identifying QTL is suggested, where several stages of diseq uilibrium mapping are used with increasingly dense marker spacing.