Systems genetics of complex traits in Drosophila melanogaster.
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.
Ayroles
Julien F
JF
Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
Carbone
Mary Anna
MA
Stone
Eric A
EA
Jordan
Katherine W
KW
Lyman
Richard F
RF
Magwire
Michael M
MM
Rollmann
Stephanie M
SM
Duncan
Laura H
LH
Lawrence
Faye
F
Anholt
Robert R H
RR
Mackay
Trudy F C
TF
D000595:Amino Acid Sequence; D000818:Animals; D017849:Animals, Inbred Strains; D001483:Base Sequence; D002874:Chromosome Mapping; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D053263:Gene Regulatory Networks / Q000502:physiology; D014644:Genetic Variation / Q000502:physiology*; D005828:Genetics, Population / Q000379:methods*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D012333:RNA, Messenger