Predicting individual differences in viral susceptibility caused by natural genetic variation within species

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 conferencePosterAcademic

Abstract

Natural genetic variation within species can underlie different individual susceptibilities upon viral infection. The molecular mechanisms by which genetic variation affects the viral susceptibility are currently poorly understood. Here we use Caenorhabditis elegans as a model organism to identify which polymorphisms alter the viral susceptibility. Moreover, we predict how the molecular mechanisms behind altered susceptibilities may work. The viral susceptibility towards Orsay virus of the commonly used lab strain, N2, is higher than that of the Hawaiian isolate CB4856. The phenotype of N2xCB4856 recombinant inbred strains was obtained by measuring the viral load upon infection and these viral loads were correlated to the genotypes by quantitative trait locus (QTL) mapping. A region on chromosome IV was found to correlate with changes in the viral susceptibility. This QTL region, containing hundreds of candidate polymorphisms, was fine mapped using two introgression line panels. The first introgression line panel contained an introgression of N2 into the genome of CB4856, whereas the second panel contained an introgression of CB4856 into the genome of N2. Using these two panels the QTL region was fine mapped to a region containing about 30 polymorphisms. Using known protein structures we predicted possible effects of candidate polymorphisms. An example is a single nucleotide polymorphism in a conserved region of the known antiviral defence gene cul-6. This polymorphism may be responsible for an altered stability of the SCF complex that targets viral particles for degradation. A causal relationship could be experimentally verified by exchanging the polymorphism of the resistant and susceptible strain, an approach we are currently taking.
Original languageEnglish
Publication statusPublished - 17 Jun 2018
EventEMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression - Barcelona, Spain
Duration: 13 Jun 201817 Jun 2018

Conference

ConferenceEMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression
CountrySpain
CityBarcelona
Period13/06/1817/06/18

Fingerprint

genetic polymorphism
introgression
genetic variation
quantitative trait loci
viral load
genome
Caenorhabditis elegans
protein structure
virion
infection
single nucleotide polymorphism
chromosomes
phenotype
viruses
degradation
genotype
organisms
genes

Cite this

van Sluijs, L., Sterken, M. G., Wang, Y. A., Ritmahan, W., Gultom, M., Pankok, F., ... Kammenga, J. E. (2018). Predicting individual differences in viral susceptibility caused by natural genetic variation within species. Poster session presented at EMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression, Barcelona, Spain.
van Sluijs, L. ; Sterken, M.G. ; Wang, Yiru A. ; Ritmahan, Wannisa ; Gultom, Mitra ; Pankok, Frederik ; Blokhina, T. ; Riksen, J.A.G. ; Volkers, J.M. ; Snoek, L.B. ; Pijlman, G.P. ; Kammenga, J.E. / Predicting individual differences in viral susceptibility caused by natural genetic variation within species. Poster session presented at EMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression, Barcelona, Spain.
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abstract = "Natural genetic variation within species can underlie different individual susceptibilities upon viral infection. The molecular mechanisms by which genetic variation affects the viral susceptibility are currently poorly understood. Here we use Caenorhabditis elegans as a model organism to identify which polymorphisms alter the viral susceptibility. Moreover, we predict how the molecular mechanisms behind altered susceptibilities may work. The viral susceptibility towards Orsay virus of the commonly used lab strain, N2, is higher than that of the Hawaiian isolate CB4856. The phenotype of N2xCB4856 recombinant inbred strains was obtained by measuring the viral load upon infection and these viral loads were correlated to the genotypes by quantitative trait locus (QTL) mapping. A region on chromosome IV was found to correlate with changes in the viral susceptibility. This QTL region, containing hundreds of candidate polymorphisms, was fine mapped using two introgression line panels. The first introgression line panel contained an introgression of N2 into the genome of CB4856, whereas the second panel contained an introgression of CB4856 into the genome of N2. Using these two panels the QTL region was fine mapped to a region containing about 30 polymorphisms. Using known protein structures we predicted possible effects of candidate polymorphisms. An example is a single nucleotide polymorphism in a conserved region of the known antiviral defence gene cul-6. This polymorphism may be responsible for an altered stability of the SCF complex that targets viral particles for degradation. A causal relationship could be experimentally verified by exchanging the polymorphism of the resistant and susceptible strain, an approach we are currently taking.",
author = "{van Sluijs}, L. and M.G. Sterken and Wang, {Yiru A.} and Wannisa Ritmahan and Mitra Gultom and Frederik Pankok and T. Blokhina and J.A.G. Riksen and J.M. Volkers and L.B. Snoek and G.P. Pijlman and J.E. Kammenga",
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van Sluijs, L, Sterken, MG, Wang, YA, Ritmahan, W, Gultom, M, Pankok, F, Blokhina, T, Riksen, JAG, Volkers, JM, Snoek, LB, Pijlman, GP & Kammenga, JE 2018, 'Predicting individual differences in viral susceptibility caused by natural genetic variation within species' EMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression, Barcelona, Spain, 13/06/18 - 17/06/18, .

Predicting individual differences in viral susceptibility caused by natural genetic variation within species. / van Sluijs, L.; Sterken, M.G.; Wang, Yiru A.; Ritmahan, Wannisa ; Gultom, Mitra; Pankok, Frederik; Blokhina, T.; Riksen, J.A.G.; Volkers, J.M.; Snoek, L.B.; Pijlman, G.P.; Kammenga, J.E.

2018. Poster session presented at EMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression, Barcelona, Spain.

Research output: Contribution to conferencePosterAcademic

TY - CONF

T1 - Predicting individual differences in viral susceptibility caused by natural genetic variation within species

AU - van Sluijs, L.

AU - Sterken, M.G.

AU - Wang, Yiru A.

AU - Ritmahan, Wannisa

AU - Gultom, Mitra

AU - Pankok, Frederik

AU - Blokhina, T.

AU - Riksen, J.A.G.

AU - Volkers, J.M.

AU - Snoek, L.B.

AU - Pijlman, G.P.

AU - Kammenga, J.E.

PY - 2018/6/17

Y1 - 2018/6/17

N2 - Natural genetic variation within species can underlie different individual susceptibilities upon viral infection. The molecular mechanisms by which genetic variation affects the viral susceptibility are currently poorly understood. Here we use Caenorhabditis elegans as a model organism to identify which polymorphisms alter the viral susceptibility. Moreover, we predict how the molecular mechanisms behind altered susceptibilities may work. The viral susceptibility towards Orsay virus of the commonly used lab strain, N2, is higher than that of the Hawaiian isolate CB4856. The phenotype of N2xCB4856 recombinant inbred strains was obtained by measuring the viral load upon infection and these viral loads were correlated to the genotypes by quantitative trait locus (QTL) mapping. A region on chromosome IV was found to correlate with changes in the viral susceptibility. This QTL region, containing hundreds of candidate polymorphisms, was fine mapped using two introgression line panels. The first introgression line panel contained an introgression of N2 into the genome of CB4856, whereas the second panel contained an introgression of CB4856 into the genome of N2. Using these two panels the QTL region was fine mapped to a region containing about 30 polymorphisms. Using known protein structures we predicted possible effects of candidate polymorphisms. An example is a single nucleotide polymorphism in a conserved region of the known antiviral defence gene cul-6. This polymorphism may be responsible for an altered stability of the SCF complex that targets viral particles for degradation. A causal relationship could be experimentally verified by exchanging the polymorphism of the resistant and susceptible strain, an approach we are currently taking.

AB - Natural genetic variation within species can underlie different individual susceptibilities upon viral infection. The molecular mechanisms by which genetic variation affects the viral susceptibility are currently poorly understood. Here we use Caenorhabditis elegans as a model organism to identify which polymorphisms alter the viral susceptibility. Moreover, we predict how the molecular mechanisms behind altered susceptibilities may work. The viral susceptibility towards Orsay virus of the commonly used lab strain, N2, is higher than that of the Hawaiian isolate CB4856. The phenotype of N2xCB4856 recombinant inbred strains was obtained by measuring the viral load upon infection and these viral loads were correlated to the genotypes by quantitative trait locus (QTL) mapping. A region on chromosome IV was found to correlate with changes in the viral susceptibility. This QTL region, containing hundreds of candidate polymorphisms, was fine mapped using two introgression line panels. The first introgression line panel contained an introgression of N2 into the genome of CB4856, whereas the second panel contained an introgression of CB4856 into the genome of N2. Using these two panels the QTL region was fine mapped to a region containing about 30 polymorphisms. Using known protein structures we predicted possible effects of candidate polymorphisms. An example is a single nucleotide polymorphism in a conserved region of the known antiviral defence gene cul-6. This polymorphism may be responsible for an altered stability of the SCF complex that targets viral particles for degradation. A causal relationship could be experimentally verified by exchanging the polymorphism of the resistant and susceptible strain, an approach we are currently taking.

M3 - Poster

ER -

van Sluijs L, Sterken MG, Wang YA, Ritmahan W, Gultom M, Pankok F et al. Predicting individual differences in viral susceptibility caused by natural genetic variation within species. 2018. Poster session presented at EMBO Workshop: C. elegans Development, Cell Biology, and Gene Expression, Barcelona, Spain.