Consequences of recombination rate variation on quantitative trait locus mapping studies: Simulations based on the Drosophila melanogaster genome

We examine the effect of variation in gene density per centimorgan on quant itative trait locus (QTL) mapping studies using data from the Drosophila me lanogaster genome project and documented regional rates of recombination. T here is tremendous variation in gene density per centimorgan across this ge nome, and we observe that this variation can cause systematic biases in QTL mapping studies. Specifically, in our simulated mapping experiments of 50 equal-effect QTL distributed randomly across the physical genome, very stro ng QTL are consistently detected near the centromeres of the two major auto somes, and few or no QTL are often detected on the Xchromosome. This patter n persisted with varying heritability, marker density, QTL effect sizes, an d transgressive segregation. Our results are consistent with empirical data Collected from QTL mapping studies of this species and its close relatives , and they explain the "small X-effect" that has been documented in genetic studies of sexual isolation in the D. melanogaster group. Because of the b iases resulting from recombination rate variation, results of QTL mapping s tudies should be taken as hypotheses to be tested by additional genetic met hods, particularly in species for which detailed genetic and physical genom e maps are not available.