Genetic variation causes differential viral susceptibilities in the model organism Caenorhabditis elegans

L. van Sluijs, M.G. Sterken, Yiru A. Wang, Wannisa Ritmahan, Mitra Gultom, Frederik Pankok, T. Blokhina, J.A.G. Riksen, J.M. Volkers, L.B. Snoek, G.P. Pijlman, J.E. Kammenga

Research output: Contribution to conferencePoster

Abstract

Individual genetic variation in the same species can cause different susceptibilities upon viral infection. Causal polymorphisms that underlie susceptibility differences can be identified by mapping the susceptibility of individuals to the genetic variants the individuals carry. Genetic mapping usually indicates a locus containing multiple candidate polymorphisms that may be the causal one. Here, we used three independent mapping populations of the nematode Caenorhabditis elegans to find a small group of candidate polymorphisms that determine the susceptibility to infection by a natural virus. Homozygous mapping populations of C. elegans were previously obtained by crossing two strains with a different viral susceptibility: the susceptible strain N2 and the more resistant strain CB4856. A recombinant inbred panel was used for quantitative trait locus (QTL) mapping to identify a region containing hundreds of candidate genes. Two introgression line panels experimentally confirmed the causal region and fine mapped the candidate region to about 30 potentially causal polymorphisms. One of these polymorphisms, the known antiviral defence gene cul-6, contains a single nucleotide polymorphism in a conserved region. We hypothesise that this polymorphism may be responsible for the difference in viral susceptibility and we are currently trying to exchange polymorphisms between the susceptible and resistant strain using CRISPR/Cas9. In the end, finding how polymorphisms in viral response pathways alter the molecular mechanisms upon viral infection can contribute to a better understanding of the close interactions between host and virus.

Original languageEnglish
Publication statusPublished - 23 May 2018
EventFEBS Workshop 2018: The molecular basis of diseases: Can we infer phenotypes from protein variant analysis? - Giorgio Prodi Hall, Bologna, Italy
Duration: 23 May 201825 May 2018

Conference

ConferenceFEBS Workshop 2018: The molecular basis of diseases: Can we infer phenotypes from protein variant analysis?
CountryItaly
CityBologna
Period23/05/1825/05/18

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van Sluijs, L., Sterken, M. G., Wang, Y. A., Ritmahan, W., Gultom, M., Pankok, F., ... Kammenga, J. E. (2018). Genetic variation causes differential viral susceptibilities in the model organism Caenorhabditis elegans. Poster session presented at FEBS Workshop 2018: The molecular basis of diseases: Can we infer phenotypes from protein variant analysis?, Bologna, Italy.