Improving quantitative trait loci mapping resolution in experimental crosses by the use of genotypically selected samples.

One of the key factors contributing to the success of a quantitative trait locus (QTL) mapping experiment is the precision with which QTL positions can be estimated. We show, using simulations, that QTL mapping precision for an experimental cross can be increased by the use of a genotypically selected sample of individuals rather than an unselected sample of the same size. Selection is performed using a previously described method that optimizes the complementarity of the crossover sites within the sample. Although the increase in precision is accompanied by a decrease in QTL detection power at markers distant from QTL, only a modest increase in marker density is needed to obtain equivalent power over the whole map. Selected samples also show a slight reduction in the number of false-positive QTL. We find that two features of selected samples independently contribute to these effects: an increase in the number of crossover sites and increased evenness in crossover spacing. We provide an empirical formula for crossover enrichment in selected samples that is useful in experimental design and data analysis. For QTL studies in which the phenotyping is more of a limiting factor than the generation of individuals and the scoring of genotypes, selective sampling is an attractive strategy for increasing genome-wide QTL map resolution.