How effects of DNA sequence variants are transmitted through intermediate endophenotypes to modulate organismal traits remains a central question in quantitative genetics. This problem can be addressed through a systems approach in a population in which genetic polymorphisms, gene expression traits, metabolites, and complex phenotypes can be evaluated on the same genotypes. Here, we focused on the metabolome, which represents the most proximal link between genetic variation and organismal phenotype, and quantified metabolite levels in 40 lines of the Drosophila melanogaster Genetic Reference Panel. We identified sex-specific modules of genetically correlated metabolites and constructed networks that integrate DNA sequence variation and variation in gene expression with variation in metabolites and organismal traits, including starvation stress resistance and male aggression. Finally, we asked to what extent SNPs and metabolites can predict trait phenotypes and generated trait- and sex-specific prediction models that provide novel insights about the metabolomic underpinnings of complex phenotypes.

中文翻译：

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果蝇代谢组的系统遗传学。

DNA 序列变异的影响如何通过中间内表型传递以调节生物体性状仍然是数量遗传学的核心问题。这个问题可以通过群体中的系统方法来解决，在这个群体中，可以在相同的基因型上评估遗传多态性、基因表达特征、代谢物和复杂表型。在这里，我们专注于代谢组，它代表了遗传变异和有机体表型之间最近的联系，并量化了黑腹果蝇遗传参考面板 40 个品系中的代谢物水平。我们确定了遗传相关代谢物的性别特异性模块，并构建了将 DNA 序列变异和基因表达变异与代谢物和生物特征变异相结合的网络，包括抗饥饿和抗雄性攻击。最后，我们询问了 SNP 和代谢物在多大程度上可以预测性状表型，并生成了性状和性别特异性预测模型，这些模型提供了关于复杂表型的代谢组学基础的新见解。