Identifying modifiers of Wnt and EGFR/RAS/MAPK signaling through quantitative C. elegans genetics

S. Maxeiner, T. Schmid, L.B. Snoek, M. Rodriguez Sanchez, F. Largey, L. van der Bent, J.E. Kammenga, A.F. Hajnal

Research output: Chapter in Book/Report/Conference proceedingAbstract


A number of studies aim at investigating the origin and potential treatment of monogenic diseases. However, polygenic diseases arising from an interplay between several malfunctioning signaling pathways are the predominant cause of up to 60% of deaths in the human population. Quantitative genetic approaches provide a powerful tool to elucidate genetic risk factors underlying such complex diseases. We use two isolates of C. elegans, N2 Bristol and CB4856 Hawaii to study the influence of naturally occurring polymorphisms on mutant genetic backgrounds well-known to promote diseases such as cancer. We chose the development of the C. elegans vulva as the phenotypic readout of Wnt and EGFR/RAS/MAPK signaling activity, where changes in signaling result in either a multivulva or vulvaless phenotype that can be quantified at single-cell resolution. Previous work has established comprehensive QTL maps spanning the entire genome. We generated these maps by comparing an N2 strain carrying a mutation in ras/let-60 or ß-catenin/bar-1 to animals carrying the let-60 or bar-1 mutation in a mixed N2/CB4856 background (so called mutation included recombinant inbred lines, miRILs). Interestingly, one QTL on the first chromosome (LGI) is shared between the two mutant backgrounds suggesting a link between Wnt and Ras signaling. We are currently identifying polymorphic modifier genes of the two pathways. To this aim, we narrow down a genomic region containing the QTL by generating N2 strains carrying well-defined CB4856 introgressions and by performing RNAi knock-down of candidate genes followed by mutant analysis.
Original languageEnglish
Title of host publicationProceedings of the FEBS-EMBO 2014
Publication statusPublished - 2014
EventFEBS-EMBO 2014 Congress, Paris, France -
Duration: 30 Aug 20144 Sept 2014


ConferenceFEBS-EMBO 2014 Congress, Paris, France


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