Low-coverage sequencing in a deep intercross of the Virginia body weight lines provides insight to the polygenic genetic architecture of growth: novel loci revealed by increased power and improved genome-coverage

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dc.contributor.authorRonneburg, T.en
dc.contributor.authorZan, Y.en
dc.contributor.authorHonaker, C. F.en
dc.contributor.authorSiegel, Paul B.en
dc.contributor.authorCarlborg, O.en
dc.date.accessioned2023-10-13T14:37:26Zen
dc.date.available2023-10-13T14:37:26Zen
dc.date.issued2023-05en
dc.description.abstractGenetic dissection of highly polygenic traits is a challenge, in part due to the power necessary to confidently identify loci with minor effects. Experi-mental crosses are valuable resources for mapping such traits. Traditionally, genome-wide analyses of experi-mental crosses have targeted major loci using data from a single generation (often the F2) with individuals from later generations being generated for replication and fine-mapping. Here, we aim to confidently identify minor-effect loci contributing to the highly polygenic basis of the long-term, bi-directional selection responses for 56-d body weight in the Virginia body weight chicken lines. To achieve this, a strategy was developed to make use of data from all generations (F2-F18) of the advanced intercross line, developed by crossing the low and high selected lines after 40 generations of selection. A cost-efficient low-coverage sequencing based approach was used to obtain high-confidence genotypes in 1Mb bins across 99.3% of the chicken genome for >3,300 intercross individuals. In total, 12 genome-wide signifi-cant, and 30 additional suggestive QTL reaching a 10% FDR threshold, were mapped for 56-d body weight. Only 2 of these QTL reached genome-wide significance in earlier analyses of the F2 generation. The minor-effect QTL mapped here were generally due to an overall increase in power by integrating data across generations, with contributions from increased genome-coverage and improved marker information content. The 12 signifi-cant QTL explain >37% of the difference between the parental lines, three times more than 2 previously reported significant QTL. The 42 significant and sugges-tive QTL together explain >80%. Making integrated use of all available samples from multiple generations in experimental crosses are economically feasible using the low-cost, sequencing-based genotyping strategies out-lined here. Our empirical results illustrate the value of this strategy for mapping novel minor-effect loci contrib-uting to complex traits to provide a more confident, comprehensive view of the individual loci that form the genetic basis of the highly polygenic, long-term selection responses for 56-d body weight in the Virginia body weight chicken lines.en
dc.description.notesWe thank Lars Ronnegard for the helpful comments and discussions regarding the stability of the minimization algorithm. The computations and data handling were enabled by resources in projects SNIC 2017/7-53, SNIC 2018-3-170 and SNIC 2020-5-14 provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement no. 2018-05973. The work was supported by the Swedish Research Council (grants 349-2005-8628, 621-2012-4634, 2017-3726 and 2018-5991) and FORMAS (grants 2013-450 and 2017-415).The Funders had no role in study design, data collec-tion and analysis, decision to publish or preparation of the manuscript.en
dc.description.sponsorshipSwedish Research Council [2013-450, 2017-415]; FORMAS; [2018-05973]; [349-2005-8628]; [621-2012-4634]; [2017-3726]; [2018-5991]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.psj.2022.102203en
dc.identifier.eissn1525-3171en
dc.identifier.issn0032-5791en
dc.identifier.issue5en
dc.identifier.other102203en
dc.identifier.pmid36907123en
dc.identifier.urihttp://hdl.handle.net/10919/116469en
dc.identifier.volume102en
dc.language.isoenen
dc.publisherElsevieren
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectQTL mappingen
dc.subjectlow-coverage sequencingen
dc.subjectbody weighten
dc.subjectadvanced intercross lineen
dc.titleLow-coverage sequencing in a deep intercross of the Virginia body weight lines provides insight to the polygenic genetic architecture of growth: novel loci revealed by increased power and improved genome-coverageen
dc.title.serialPoultry Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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