The genetic architecture of the transcriptional response to heat-shock in C. elegans

M.G. Sterken, L.B. Snoek, R.P.J. Bevers, R. Brenchley, A. van 't Hof, A.R. Cossins, J.E. Kammenga

Research output: Chapter in Book/Report/Conference proceedingAbstractAcademic

Abstract

The genetic architecture of the transcriptional response to heat-shock in C. elegans Mark G Sterken¹, L Basten Snoek¹, Roel P J Bevers¹, Rachel C Brenchley², Arjen E van 't Hof², Andrew R Cossins², Jan E Kammenga¹ 1Wageningen University, Laboratory of Nematology, Wageningen, 6708PB, Netherlands, 2University of Liverpool, Centre for Genomic Research, Liverpool, L69 7ZB, United Kingdom The basis for natural selection is variation and ultimately phenotypic variation is caused by differences between genotypes. Through genotypic variation organisms can be better equipped to handle (environmental) stress. This phenotypic plasticity, which is an important ability to cope with changing environmental conditions, can have a genetic source. However, most experimental work on C. elegans is conducted under ‘standard culturing conditions’ with a limited range of genotypes. Generally the genotypes used are restricted to wild type N2 and mutants in an N2 background, excluding detection of (more subtle) effects due to natural variation and differences in genetic background. Consequently, little is known about the variation in the components of genetic pathways within natural populations. Here, we investigated the influence of genetic variation on the transcriptional response to ambient heat-stress. Genetic variation between the genetically most divergent C. elegans isolates, N2 and CB4856, was perturbed and captured in a set of recombinant inbred lines (RILs) (Li et al., 2006). These RILs were exposed to a 2 hour heat-shock of 35oC. After which the genome- wide transcript levels were measured for all individual RILs. Quantitative trait locus mapping was applied to find the genomic loci that underlie the variation in transcriptional responses between the RILs. These heat-shock expression-QTLs (eQTLs) were compared to the eQTLs found in a control group that did not receive a heat-shock. Thereafter the experiment was independently repeated in an introgression line population, in which the lines only contain a single small introgression of CB4856 in an N2 background (Doroszuk et al. 2009). This allowed us to biologically validate the genotypic effects on gene expression found in the RIL population. We found that the genome-wide transcriptional response to heat-stress is highly regulated. Furthermore the regulated genes (those with an eQTL) and the location of the regulators were confirmed to a high degree in the introgression lines. This result provides a unique insight in the robustness of quantitative genetic analyses and shows the biologic relevance of its outcomes. Li et al. (2006) Plos Genetics 2(12): e222 Doroszuk et al. (2009) NAR 37: 16, e110 Funded by ERASysBio+ project GRAPPLE - Iterative modelling of gene regulatory interactions underlying stress, disease and ageing in C. elegans
Original languageEnglish
Title of host publicationAbstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012
Pages102-102
Publication statusPublished - 2012
EventEvolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA -
Duration: 3 Apr 20126 Apr 2012

Conference

ConferenceEvolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA
Period3/04/126/04/12

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heat stress
inbred lines
quantitative trait loci
introgression
genotype
nematology
genomics
genetic variation
genome
quantitative genetics
regulator genes
phenotypic plasticity
phenotypic variation
genetic background
natural selection
United Kingdom
Netherlands
gene expression
mutants
loci

Cite this

Sterken, M. G., Snoek, L. B., Bevers, R. P. J., Brenchley, R., van 't Hof, A., Cossins, A. R., & Kammenga, J. E. (2012). The genetic architecture of the transcriptional response to heat-shock in C. elegans. In Abstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012 (pp. 102-102)
Sterken, M.G. ; Snoek, L.B. ; Bevers, R.P.J. ; Brenchley, R. ; van 't Hof, A. ; Cossins, A.R. ; Kammenga, J.E. / The genetic architecture of the transcriptional response to heat-shock in C. elegans. Abstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012. 2012. pp. 102-102
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Sterken, MG, Snoek, LB, Bevers, RPJ, Brenchley, R, van 't Hof, A, Cossins, AR & Kammenga, JE 2012, The genetic architecture of the transcriptional response to heat-shock in C. elegans. in Abstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012. pp. 102-102, Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3/04/12.

The genetic architecture of the transcriptional response to heat-shock in C. elegans. / Sterken, M.G.; Snoek, L.B.; Bevers, R.P.J.; Brenchley, R.; van 't Hof, A.; Cossins, A.R.; Kammenga, J.E.

Abstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012. 2012. p. 102-102.

Research output: Chapter in Book/Report/Conference proceedingAbstractAcademic

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AU - Bevers, R.P.J.

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AU - van 't Hof, A.

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N2 - The genetic architecture of the transcriptional response to heat-shock in C. elegans Mark G Sterken¹, L Basten Snoek¹, Roel P J Bevers¹, Rachel C Brenchley², Arjen E van 't Hof², Andrew R Cossins², Jan E Kammenga¹ 1Wageningen University, Laboratory of Nematology, Wageningen, 6708PB, Netherlands, 2University of Liverpool, Centre for Genomic Research, Liverpool, L69 7ZB, United Kingdom The basis for natural selection is variation and ultimately phenotypic variation is caused by differences between genotypes. Through genotypic variation organisms can be better equipped to handle (environmental) stress. This phenotypic plasticity, which is an important ability to cope with changing environmental conditions, can have a genetic source. However, most experimental work on C. elegans is conducted under ‘standard culturing conditions’ with a limited range of genotypes. Generally the genotypes used are restricted to wild type N2 and mutants in an N2 background, excluding detection of (more subtle) effects due to natural variation and differences in genetic background. Consequently, little is known about the variation in the components of genetic pathways within natural populations. Here, we investigated the influence of genetic variation on the transcriptional response to ambient heat-stress. Genetic variation between the genetically most divergent C. elegans isolates, N2 and CB4856, was perturbed and captured in a set of recombinant inbred lines (RILs) (Li et al., 2006). These RILs were exposed to a 2 hour heat-shock of 35oC. After which the genome- wide transcript levels were measured for all individual RILs. Quantitative trait locus mapping was applied to find the genomic loci that underlie the variation in transcriptional responses between the RILs. These heat-shock expression-QTLs (eQTLs) were compared to the eQTLs found in a control group that did not receive a heat-shock. Thereafter the experiment was independently repeated in an introgression line population, in which the lines only contain a single small introgression of CB4856 in an N2 background (Doroszuk et al. 2009). This allowed us to biologically validate the genotypic effects on gene expression found in the RIL population. We found that the genome-wide transcriptional response to heat-stress is highly regulated. Furthermore the regulated genes (those with an eQTL) and the location of the regulators were confirmed to a high degree in the introgression lines. This result provides a unique insight in the robustness of quantitative genetic analyses and shows the biologic relevance of its outcomes. Li et al. (2006) Plos Genetics 2(12): e222 Doroszuk et al. (2009) NAR 37: 16, e110 Funded by ERASysBio+ project GRAPPLE - Iterative modelling of gene regulatory interactions underlying stress, disease and ageing in C. elegans

AB - The genetic architecture of the transcriptional response to heat-shock in C. elegans Mark G Sterken¹, L Basten Snoek¹, Roel P J Bevers¹, Rachel C Brenchley², Arjen E van 't Hof², Andrew R Cossins², Jan E Kammenga¹ 1Wageningen University, Laboratory of Nematology, Wageningen, 6708PB, Netherlands, 2University of Liverpool, Centre for Genomic Research, Liverpool, L69 7ZB, United Kingdom The basis for natural selection is variation and ultimately phenotypic variation is caused by differences between genotypes. Through genotypic variation organisms can be better equipped to handle (environmental) stress. This phenotypic plasticity, which is an important ability to cope with changing environmental conditions, can have a genetic source. However, most experimental work on C. elegans is conducted under ‘standard culturing conditions’ with a limited range of genotypes. Generally the genotypes used are restricted to wild type N2 and mutants in an N2 background, excluding detection of (more subtle) effects due to natural variation and differences in genetic background. Consequently, little is known about the variation in the components of genetic pathways within natural populations. Here, we investigated the influence of genetic variation on the transcriptional response to ambient heat-stress. Genetic variation between the genetically most divergent C. elegans isolates, N2 and CB4856, was perturbed and captured in a set of recombinant inbred lines (RILs) (Li et al., 2006). These RILs were exposed to a 2 hour heat-shock of 35oC. After which the genome- wide transcript levels were measured for all individual RILs. Quantitative trait locus mapping was applied to find the genomic loci that underlie the variation in transcriptional responses between the RILs. These heat-shock expression-QTLs (eQTLs) were compared to the eQTLs found in a control group that did not receive a heat-shock. Thereafter the experiment was independently repeated in an introgression line population, in which the lines only contain a single small introgression of CB4856 in an N2 background (Doroszuk et al. 2009). This allowed us to biologically validate the genotypic effects on gene expression found in the RIL population. We found that the genome-wide transcriptional response to heat-stress is highly regulated. Furthermore the regulated genes (those with an eQTL) and the location of the regulators were confirmed to a high degree in the introgression lines. This result provides a unique insight in the robustness of quantitative genetic analyses and shows the biologic relevance of its outcomes. Li et al. (2006) Plos Genetics 2(12): e222 Doroszuk et al. (2009) NAR 37: 16, e110 Funded by ERASysBio+ project GRAPPLE - Iterative modelling of gene regulatory interactions underlying stress, disease and ageing in C. elegans

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BT - Abstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012

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Sterken MG, Snoek LB, Bevers RPJ, Brenchley R, van 't Hof A, Cossins AR et al. The genetic architecture of the transcriptional response to heat-shock in C. elegans. In Abstracts of papers presented at the Evolution of Caenorhabditis and Other Nematodes, Cold Spring Harbor Laboratory, New York, USA, 3-6 April 2012. 2012. p. 102-102