Viral susceptibility differs between individuals due to genetic and environmental differences. Currently, the molecular mechanisms underlying differences in individual susceptibility are poorly understood. Here, we use the model organism Caenorhabditis elegans to unravel molecular pathways affected by genetic polymorphisms that lead to differences in susceptibility of an individual. Two distinct genotypes, N2 and CB4856, differ in viral susceptibility to infection by Orsay virus. Here, we used quantitative trait loci (QTL) mapping in N2xCB4856 recombinant inbred lines (RILs) in order to identify loci affecting susceptibility. We found two genomic loci correlated with viral susceptibility. Introgression lines (ILs) containing single genetic fragments of one parental strain in the genetic background of the other strain were used to finemap the genetic loci. After infection of a panel of ILs, the QTL region could be narrowed down to a region containing about 30 polymorphic genes. We selected genes using literature data and databases that predict the structure and function of proteins. The selected candidate polymorphisms found by the analysis will be targeted by CRISPR-Cas9 to exchange specific alleles between the parental strains. In the end, this approach can help to unravel how genetic polymorphisms can determine the viral susceptibility of an individual.
There are no comments yet. You can post the first one!
Post a comment
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.