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Nat Genet. 2009 Mar;41(3):299-307. doi: 10.1038/ng.332. Epub 2009 Feb 22.

Systems genetics of complex traits in Drosophila melanogaster.

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1
Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.

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.

PMID:
19234471
PMCID:
PMC2752214
DOI:
10.1038/ng.332
[Indexed for MEDLINE]
Free PMC Article
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