Beyond induced mutants: using worms to study natural variation in genetic pathways

Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease.