Article abstract
Nature Genetics 41, 299 - 307 (2009)
Published online: 22 February 2009 | doi:10.1038/ng.332
Systems genetics of complex traits in Drosophila melanogaster
Julien F Ayroles1,2,6, Mary Anna Carbone1,2,6, Eric A Stone3,6, Katherine W Jordan1,2, Richard F Lyman1,2, Michael M Magwire1,2,5, Stephanie M Rollmann1,2,5, Laura H Duncan1,2, Faye Lawrence1,2, Robert R H Anholt1,2,4 & Trudy F C Mackay1,2
Abstract
Determining the genetic architecture of complex traits is challenging because phenotypic variation arises from interactions between multiple, environmentally sensitive alleles. We quantified genome-wide transcript abundance and phenotypes for six ecologically relevant traits in D. melanogaster wild-derived inbred lines. We observed 10,096 genetically variable transcripts and high heritabilities for all organismal phenotypes. The transcriptome is highly genetically intercorrelated, forming 241 transcriptional modules. Modules are enriched for transcripts in common pathways, gene ontology categories, tissue-specific expression and transcription factor binding sites. The high degree of transcriptional connectivity allows us to infer genetic networks and the function of predicted genes from annotations of other genes in the network. Regressions of organismal phenotypes on transcript abundance implicate several hundred candidate genes that form modules of biologically meaningful correlated transcripts affecting each phenotype. Overlapping transcripts in modules associated with different traits provide insight into the molecular basis of pleiotropy between complex traits.
- Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
- W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.
- Department of Statistics, North Carolina State University, Raleigh, North Carolina 27695, USA.
- Department of Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.
- Present addresses: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK (M.M.M.) and Department of Biological Sciences, University of Cincinnati, PO Box 210006, 614 Rieveschl Hall, Cincinnati, Ohio 45221, USA (S.M.R.).
- These authors contributed equally to this work.
Correspondence to: Trudy F C Mackay1,2 e-mail: trudy_mackay@ncsu.edu
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