Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster.
Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster.
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DOI：
10.1186/1471-2164-10-124
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发表时间：
2009-03-24
期刊：
影响因子：
4.4
通讯作者：
McIntyre LM
中科院分区：
文献类型：
--
作者：
Nuzhdin SV;Brisson JA;Pickering A;Wayne ML;Harshman LG;McIntyre LM
基于分子过程的基因型-表型图谱将最终使我们能够预测个体间的遗传变异如何导致表型改变。然而，绘制这样一幅地图远非易事。它需要了解分子变异如何重塑发育和代谢网络，以及这些网络的功能状态如何以基因型特异性方式改变表型。我们专注于后一个问题，通过描述72个果蝇基因型之间的InR/TOR途径的基因转录水平的遗传变异。我们观察到紧密的协方差在转录水平的基因不知道通过直接转录控制相互影响。我们总结了转录组的变化与因素分析，并观察到强大的协方差内的dFOXO分支和TOR分支的途径的基因表达。最后，我们调查是否转录组变异的主轴形状表型预期通过InR/TOR途径的影响。我们发现有限的证据表明，在InR/TOR通路中的单个上游基因的转录水平以预期的方式预测苍蝇表型。然而，没有证据表明这些影响是通过下游转录组变异的主轴介导的。总之，我们的研究结果质疑遗传网络的“稀疏”性质的断言，同时验证和扩展候选基因的方法在复杂性状的分析。
A molecular process based genotype-to-phenotype map will ultimately enable us to predict how genetic variation among individuals results in phenotypic alterations. Building such a map is, however, far from straightforward. It requires understanding how molecular variation re-shapes developmental and metabolic networks, and how the functional state of these networks modifies phenotypes in genotype specific way. We focus on the latter problem by describing genetic variation in transcript levels of genes in the InR/TOR pathway among 72 Drosophila melanogaster genotypes. We observe tight co-variance in transcript levels of genes not known to influence each other through direct transcriptional control. We summarize transcriptome variation with factor analyses, and observe strong co-variance of gene expression within the dFOXO-branch and within the TOR-branch of the pathway. Finally, we investigate whether major axes of transcriptome variation shape phenotypes expected to be influenced through the InR/TOR pathway. We find limited evidence that transcript levels of individual upstream genes in the InR/TOR pathway predict fly phenotypes in expected ways. However, there is no evidence that these effects are mediated through the major axes of downstream transcriptome variation. In summary, our results question the assertion of the 'sparse' nature of genetic networks, while validating and extending candidate gene approaches in the analyses of complex traits.
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影响因子：
12.3
作者：
McIntyre LM;Bono LM;Genissel A;Westerman R;Junk D;Telonis-Scott M;Harshman L;Wayne ML;Kopp A;Nuzhdin SV
通讯作者：
Nuzhdin SV
影响因子：
12.3
作者：
Curtis C;Landis GN;Folk D;Wehr NB;Hoe N;Waskar M;Abdueva D;Skvortsov D;Ford D;Luu A;Badrinath A;Levine RL;Bradley TJ;Tavaré S;Tower J
通讯作者：
Tower J
影响因子：
2.7
作者：
Hersh, Bradley M.;Nelson, Craig E.;Carroll, Sean B.
通讯作者：
Carroll, Sean B.
影响因子：
64.8
作者：
Morris, JZ;Tissenbaum, HA;Ruvkun, G
通讯作者：
Ruvkun, G
影响因子：
9.2
作者：
Kapahi, P;Zid, BM;Benzer, S
通讯作者：
Benzer, S