Fine-mapping natural alleles: quantitative complementation to the rescue

Mapping the genes responsible for natural variation and divergence is a challenging task. Many studies have mapped genes to genomic regions or generated lists of candidates, but few studies have implicated specific genes with a high standard of evidence. I propose that combining recent advances in genomic engineering with a modified version of the quantitative complementation test will help turn candidate genes into causal genes. By creating loss‐of‐function mutations in natural strains, and using these mutations to quantitatively fail‐to‐complement natural alleles, fine mapping should be greatly facilitated. As an example, I propose that the CRISPR/Cas9 system could be combined with the FLP/FRT system to fine‐map genes in the numerous systems where inversions have frustrated these efforts.