Fast genetic mapping of complex traits in C. elegans using millions of individuals in bulk

Genetic studies of complex traits in animals have been hindered by the need to generate, maintain, and phenotype large panels of recombinant lines. We developed a new method, C. elegans eXtreme Quantitative Trait Locus (ceX-QTL) mapping, that overcomes this obstacle via bulk selection on millions of unique recombinant individuals. We used ceX-QTL to map a drug resistance locus with high resolution. We also mapped differences in gene expression in live worms and discovered a regulatory feedback loop that responds to changes in HSP-90 chaperone activity. Lastly, we used ceX-QTL to map loci that influence fitness and discovered that one such locus is caused by a deletion in a highly conserved chromatin reader in the N2 reference strain. ceX-QTL is fast, powerful and cost-effective, and will accelerate the study of complex traits in animals.