Systems genetics of complex traits in Drosophila melanogaster.

Systems genetics of complex traits in Drosophila melanogaster.
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DOI:
10.1038/ng.332
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发表时间:
2009-03
期刊:
影响因子:
30.8
通讯作者:
Mackay, Trudy F. C.
Mackay, Trudy F. C.
中科院分区:
生物学1区
文献类型:
--
作者:
Ayroles, Julien F.;Carbone, Mary Anna;Stone, Eric A.;Jordan, Katherine W.;Lyman, Richard F.;Magwire, Michael M.;Rollmann, Stephanie M.;Duncan, Laura H.;Lawrence, Faye;Anholt, Robert R. H.;Mackay, Trudy F. C.

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确定复杂性状的遗传结构具有挑战性,因为表型变异来自多个环境敏感等位基因之间的相互作用。我们定量了D.黑腹果蝇野生衍生的近交系。我们观察到10,096个遗传可变的转录本和所有生物表型的高遗传率。转录组在遗传上高度相关,形成241个转录模块。模块中富集了常见途径中的转录物、基因本体论类别、组织特异性表达和转录因子结合位点。高转录连接性使我们能够推断遗传网络和预测基因的功能,基于网络中其他基因的注释。生物体表型对转录本丰度的回归涉及数百个候选基因,这些基因形成影响每个表型的具有生物学意义的相关转录本的模块。与不同性状相关的模块中的重叠转录本提供了对复杂性状之间多效性的分子基础的深入了解。
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 inter-correlated, 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 transcriptional connectivity allows us to infer genetic networks and the function of predicted genes based on 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 provides insight into the molecular basis of pleiotropy between complex traits.
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