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Polygenicity and Epistasis Underlie Fitness-Proximal Traits in the Caenorhabditis elegans Multiparental Experimental Evolution (CeMEE) Panel

2017-12-04Preprint Open access
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dc.contributor.authorNoble, Luke M
dc.contributor.authorChelo, Ivo
dc.contributor.authorGuzella, Thiago
dc.contributor.authorAfonso, Bruno
dc.contributor.authorRiccardi, David D
dc.contributor.authorAmmerman, Patrick
dc.contributor.authorDayarian, Adel
dc.contributor.authorCarvalho, Sara
dc.contributor.authorCrist, Anna
dc.contributor.authorPino-Querido, Ania
dc.contributor.authorShraiman, Boris
dc.contributor.authorRockman, Matthew V
dc.contributor.authorTeotónio, Henrique
dc.date.accessioned2017-12-05T17:21:49Z
dc.date.available2018-12-04T01:30:08Z
dc.date.issued2017-12-04
dc.descriptionThe deposited article is a pre-print version and it has not been submitted to peer reviewing. This article version was provided by bioRxiv and is the preprint first posted online Mar. 26, 2017. This publication hasn't any creative commons license associated. The deposited article version contains attached the supplementary materials within the pdf.pt_PT
dc.description.abstractUnderstanding the genetic basis of complex traits remains a major challenge in biology. Polygenicity, phenotypic plasticity and epistasis contribute to phenotypic variance in ways that are rarely clear. This uncertainty can be problematic for estimating heritability, for predicting individual phenotypes from genomic data, and for parameterizing models of phenotypic evolution. Here we report an advanced recombinant inbred line (RIL) quantitative trait locus (QTL) mapping panel for the hermaphroditic nematode Caenorhabditis elegans, the C. elegans multiparental experimental evolution (CeMEE) panel. The CeMEE panel, comprising 507 RILs at present, was created by hybridization of 16 wild isolates, experimental evolution for 140-190 generations, and inbreeding by selfing for 13-16 generations. The panel contains 22% of single nucleotide polymorphisms known to segregate in natural populations, and complements existing C. elegans mapping resources by providing fine resolution and high nucleotide diversity across >95% of the genome. We apply it to study the genetic basis of two fitness components, fertility and hermaphrodite body size at time of reproduction, with high broad sense heritability in the CeMEE. While simulations show we should detect common alleles with additive effects as small as 5%, at gene-level resolution, the genetic architectures of these traits does not feature such alleles. We instead find that a significant fraction of trait variance, approaching 40% for fertility, can be explained by sign epistasis with main effects below the detection limit. In congruence, phenotype prediction from genomic similarity, while generally poor (r2 < 10%), requires modeling epistasis for optimal accuracy, with most variance attributed to the rapidly evolving chromosome arms.pt_PT
dc.description.sponsorshipNational Science Foundation grant: (PHY-1125915); National Institutes of Health grants: (R25-GM-067110, R01-GM-089972, R01-GM-121828); Gordon and Betty Moore Foundation grant: (2919.01); Human Frontiers Science Program (RGP0045/2010); European Research Council grant: (FP7/2007-2013/243285); Agence Nationale de la Recherche grant: (ANR-14-ACHN-0032-01).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPolygenicity and Epistasis Underlie Fitness-Proximal Traits in the Caenorhabditis elegans Multiparental Experimental Evolution (CeMEE) Panel View ORCID ProfileLuke M. Noble, View ORCID ProfileIvo Chelo, Thiago Guzella, Bruno Afonso, David D. Riccardi, Patrick Ammerman, Adel Dayarian, Sara Carvalho, Anna Crist, Ania Pino-Querido, View ORCID ProfileBoris Shraiman, View ORCID ProfileMatthew V. Rockman and Henrique Teotónio Genetics December 1, 2017 vol. 207 no. 4 1663-1685; https://doi.org/10.1534/genetics.117.300406pt_PT
dc.identifier.doi10.1534/genetics.117.300406pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/815
dc.language.isoengpt_PT
dc.peerreviewednopt_PT
dc.publisherGenetics Society of Americapt_PT
dc.relationPHY-1125915pt_PT
dc.relationR25-GM-067110pt_PT
dc.relation2919.01pt_PT
dc.relationR01-GM-089972pt_PT
dc.relationR01-GM-121828pt_PT
dc.relationRGP0045/2010pt_PT
dc.relationA study on the interaction among natural selection, mutation and recombination, with Caenorhabditis elegans experimental evolution
dc.relation.publisherversionhttp://www.genetics.org/content/207/4/1663pt_PT
dc.subjectgenetic architecturept_PT
dc.subjectpolygenicitypt_PT
dc.subjectepistasispt_PT
dc.subjectexperimental evolutionpt_PT
dc.subjectbody sizept_PT
dc.subjectfertilitypt_PT
dc.subjectselfingpt_PT
dc.subjectGWASpt_PT
dc.subjectheritabilitypt_PT
dc.subjectquantitative traitpt_PT
dc.subjectcomplex traitpt_PT
dc.subjectQTLpt_PT
dc.subjectMPPpt_PT
dc.subjectmultiparental populationspt_PT
dc.subjectMultiparent Advanced Generation Inter-Cross (MAGIC)pt_PT
dc.titlePolygenicity and Epistasis Underlie Fitness-Proximal Traits in the Caenorhabditis elegans Multiparental Experimental Evolution (CeMEE) Panelpt_PT
dc.typepreprint
dspace.entity.typePublication
oaire.awardTitleA study on the interaction among natural selection, mutation and recombination, with Caenorhabditis elegans experimental evolution
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/243285/EU
oaire.citation.endPage1685pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage1663pt_PT
oaire.citation.titleGeneticspt_PT
oaire.citation.volume207pt_PT
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.embargofctThe deposited article has 12 months of embargo period in terms of access, because of the journal's policies and the publisher's copyright policy, which require a period of embargo of 12 months of duration since the released date of the publication.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typepreprintpt_PT
relation.isProjectOfPublicationf192fb79-7c0d-434b-b3b3-0b3399301ee3
relation.isProjectOfPublication.latestForDiscoveryf192fb79-7c0d-434b-b3b3-0b3399301ee3

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