title: A Powerful New Quantitative Genetics Platform, Combining Caenorhabditis elegans High-Throughput Fitness Assays with a Large Collection of Recombinant Strains.
abstract: The genetic variants underlying complex traits are often elusive even in powerful model organisms such as Caenorhabditis elegans with controlled genetic backgrounds and environmental conditions. Two major contributing factors are: (1) the lack of statistical power from measuring the phenotypes of small numbers of individuals, and (2) the use of phenotyping platforms that do not scale to hundreds of individuals and are prone to noisy measurements. Here, we generated a new resource of 359 recombinant inbred strains that augments the existing C. elegans N2xCB4856 recombinant inbred advanced intercross line population. This new strain collection removes variation in the neuropeptide receptor gene npr-1, known to have large physiological and behavioral effects on C. elegans and mitigates the hybrid strain incompatibility caused by zeel-1 and peel-1, allowing for identification of quantitative trait loci that otherwise would have been masked by those effects. Additionally, we optimized highly scalable and accurate high-throughput assays of fecundity and body size using the COPAS BIOSORT large particle nematode sorter. Using these assays, we identified quantitative trait loci involved in fecundity and growth under normal growth conditions and after exposure to the herbicide paraquat, including independent genetic loci that regulate different stages of larval growth. Our results offer a powerful platform for the discovery of the genetic variants that control differences in responses to drugs, other aqueous compounds, bacterial foods, and pathogenic stresses.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208 erik.andersen@northwestern.edu lkruglyak@mednet.ucla.edu.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Andersen
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Shimko
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Crissman
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: Howard Hughes Medical Institute, Departments of Human Genetics and Biological Chemistry, David Geffen School of Medicine, U.C.L.A., Los Angeles, California 90095.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Bloom
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544.
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Seidel
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Gerke
authors.affiliation: Howard Hughes Medical Institute, Departments of Human Genetics and Biological Chemistry, David Geffen School of Medicine, U.C.L.A., Los Angeles, California 90095 erik.andersen@northwestern.edu lkruglyak@mednet.ucla.edu.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D002874:Chromosome Mapping; D056084:Genetic Fitness; D008040:Genetic Linkage; D006540:Herbicides / Q000494:pharmacology; D008957:Models, Genetic; D010641:Phenotype; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D011995:Recombination, Genetic
chemical_list: D006540:Herbicides
keywords: C. elegans; QTL mapping; fitness assays; high-throughput phenotyping