Despite decades of research, the genetic architecture underlying most complex traits – traits with contribution of multiple genetic and environmental factors – remains poorly understood. Many factors, including complex population structure, difficulty in acquiring large sample sizes, genetic heterogeneity and others, have complicated the study of complex traits in humans, and model organisms have provided an excellent tool for studying such traits. In C. elegans, quantitative trait loci (QTL) mapping has been used to identify genetic variation between strains that underlie many aspects of the worm’s physiology and behavior. So far, QTL mapping in C. elegans has been performed using panels of recombinant inbred lines (RILs). Such panels, while providing an excellent tool for mapping differences across strains, are usually limited to comparisons across two backgrounds, and are arduous to generate, limiting the scalability of the approach to multiple strain backgrounds or transgenic animals.
To deal with these limitations, we developed a bulk segregant approach for mapping genetic traits in C. elegans. Our approach is based on mutants in which reproduction is obligate sexual, that are allowed to mate for multiple generations. The resultant segregant pool can be subjected to selection, and groups of segregants showing differential phenotypes can be used for mapping. Using simulations, we compared the power of this approach to other mapping approaches under different assmuptions. We then applied this method to a cross between the lab Bristol (N2) strain and a wild Hawaii isolate (CB4856), and identified QTLs associated with fitness. Finally, in a cross between two transgenic strains under different backgrounds, we identified a distant-acting QTL underlying differences in the expression of a fluorescent marker.