Influence of marker heterozygosity and genetic heterogeneity on fine mapping

The purpose of the current study was to utilize the Genetic Analysis Worksh op 12 simulated data to evaluate fine-mapping strategies for quantitative t raits. We approached the analysis as if it was a follow-up to a genome scan that had identified two regions of interest and used the provided 1-cM den sity microsatellite typing data to mimic fine mapping of these regions. As these investigators knew the true locations of the putative genes under stu dy, we explored the effects of the informativeness of microsatellite marker s (marker heterozygosity) and the effects of genetic heterogeneity across f amilies for ten replicates of the data. These results shed a cautionary lig ht on the reliability of fine-mapping efforts on refining mapping locations as the position and the strength of the lod score can be markedly affected by the sampling of the population, the amount of variation accounted for b y the gene, and the informativeness of the marker. Our studies did not reve al a large effect of unlinked families on the shape of the lod score peak. ((C)) 2001 Wiley-Liss, Inc.