A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits

B.L. Snoek, J.M. Volkers, H. Nijveen, Carola Petersen, Philipp Dirksen, M.G. Sterken, Rania Nakad, J.A.G. Riksen, P.C. Rosenstiel, J.J. Stastna, B.P. Braekman, S.C. Harvey, Hinrich Schulenburg, J.E. Kammenga

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Abstract

Background - The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale.
Results - To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping.
Conclusion -Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs.
Original languageEnglish
Article number24
Number of pages17
JournalBMC Biology
Volume17
DOIs
Publication statusPublished - 12 Mar 2019

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life history trait
inbred lines
quantitative trait loci
genotype
life history
genetic variation
Quantitative Trait Loci
Pathogens
Polymorphism
Caenorhabditis elegans
Population
Genotype
Genes
RNA
stress resistance
local adaptation
Single Nucleotide Polymorphism
nematode
population growth
polymorphism

Cite this

Snoek, B.L. ; Volkers, J.M. ; Nijveen, H. ; Petersen, Carola ; Dirksen, Philipp ; Sterken, M.G. ; Nakad, Rania ; Riksen, J.A.G. ; Rosenstiel, P.C. ; Stastna, J.J. ; Braekman, B.P. ; Harvey, S.C. ; Schulenburg, Hinrich ; Kammenga, J.E. / A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits. In: BMC Biology. 2019 ; Vol. 17.
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abstract = "Background - The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale.Results - To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping.Conclusion -Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs.",
author = "B.L. Snoek and J.M. Volkers and H. Nijveen and Carola Petersen and Philipp Dirksen and M.G. Sterken and Rania Nakad and J.A.G. Riksen and P.C. Rosenstiel and J.J. Stastna and B.P. Braekman and S.C. Harvey and Hinrich Schulenburg and J.E. Kammenga",
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A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits. / Snoek, B.L.; Volkers, J.M.; Nijveen, H.; Petersen, Carola; Dirksen, Philipp; Sterken, M.G.; Nakad, Rania; Riksen, J.A.G.; Rosenstiel, P.C.; Stastna, J.J.; Braekman, B.P.; Harvey, S.C.; Schulenburg, Hinrich; Kammenga, J.E.

In: BMC Biology, Vol. 17, 24, 12.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits

AU - Snoek, B.L.

AU - Volkers, J.M.

AU - Nijveen, H.

AU - Petersen, Carola

AU - Dirksen, Philipp

AU - Sterken, M.G.

AU - Nakad, Rania

AU - Riksen, J.A.G.

AU - Rosenstiel, P.C.

AU - Stastna, J.J.

AU - Braekman, B.P.

AU - Harvey, S.C.

AU - Schulenburg, Hinrich

AU - Kammenga, J.E.

PY - 2019/3/12

Y1 - 2019/3/12

N2 - Background - The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale.Results - To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping.Conclusion -Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs.

AB - Background - The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale.Results - To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping.Conclusion -Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs.

U2 - 10.1186/s12915-019-0642-8

DO - 10.1186/s12915-019-0642-8

M3 - Article

VL - 17

JO - BMC Biology

JF - BMC Biology

SN - 1741-7007

M1 - 24

ER -