Unveiling cryptic genetic variation in C. elegans

Unveiling cryptic genetic variation in C. elegans Jan Kammenga¹ 1Wageningen University, Nematology, Wageningen, 6708PB, Netherlands Over the past few decades research in C. elegans has been at the forefront of genetic and evolutionary research. Genetic analysis in C. elegans is rooted in forward and reverse genetic screens using the standard laboratory wild type strain N2. Mutant knock-out and RNAi screens have served as most valuable platforms for pathway analysis, gene detection and functional analysis. Yet, these studies do not yield insight into the natural variation of pathways or the subtle allelic effects of polymorphic genes. Therefore increased efforts have been made to explore the genetic landscape of natural C. elegans populations and to identify the natural polymorphisms affecting a range of complex traits. Compared to other model species, C. elegans, is lagging behind in terms of quantitative trait analysis. But the worm offers the unique opportunity to combine reverse and forward genetic screens with the power of natural genetic variation using well established recombinant inbred lines derived from a cross between N2 and CB4856. I will highlight these new developments and its potentials compared to classic complex trait mapping. Various genetic perturbation experiments using RNAi are possible in these RILs, even though CB4856 is not sensitive to RNAi. Further I will show the power of forward genetic screens using mutant-RIL populations at the transcriptome level. Both RNAi and induced mutations combined with natural variation enable a targeted investigation of cryptic variation underlying complex traits.