Causes and Consequences of Genetic Background Effects Illuminated by Integrative Genomic Analysis
Causes and Consequences of Genetic Background Effects Illuminated by Integrative Genomic Analysis
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DOI：
10.1534/genetics.113.159426
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发表时间：
2014-04-01
期刊：
影响因子：
3.3
通讯作者：
Dworkin, Ian
中科院分区：
文献类型：
--
作者：
Chandler, Christopher H.;Chari, Sudarshan;Dworkin, Ian
个体突变的表型结果受其发生的野生型遗传背景的调节。虽然这种背景依赖性被广泛观察到，但我们不知道是否存在跨物种和性状的一般模式，也不知道其背后的机制，我们也缺乏关于突变如何与遗传背景相互作用以影响基因表达以及这反过来又如何介导突变表型的知识。此外，遗传背景如何影响上位性模式仍不清楚。为了研究果蝇翅上扇形（E3）等位基因遗传背景依赖性的遗传基础和基因组后果，我们从基因渗入作图实验和标记的RNA基因表达数据集生成了多个新的基因组水平数据集。此外，我们使用了全基因组重测序的父母线，两个常用的实验室菌株预测多态性转录因子结合位点的SD。我们将这些数据与先前发表的来自表达微阵列和修饰突变筛选的基因组数据集进行了整合。通过在多个数据集中搜索显示一致信号的基因，我们能够识别出一组强大的候选基因座，这些基因座有助于sd突变的背景依赖性效应。我们还表明，以前报道的大多数背景依赖性修饰剂是由高阶上位性引起的，而不是定量非互补。这些研究结果提供了一个有用的基础，更详细的调查遗传背景的依赖，在这个系统中，这种方法很可能被证明是有用的，在探索其他性状的遗传基础。
The phenotypic consequences of individual mutations are modulated by the wild-type genetic background in which they occur. Although such background dependence is widely observed, we do not know whether general patterns across species and traits exist or about the mechanisms underlying it. We also lack knowledge on how mutations interact with genetic background to influence gene expression and how this in turn mediates mutant phenotypes. Furthermore, how genetic background influences patterns of epistasis remains unclear. To investigate the genetic basis and genomic consequences of genetic background dependence of the scalloped(E3) allele on the Drosophila melanogaster wing, we generated multiple novel genome-level datasets from a mapping-by-introgression experiment and a tagged RNA gene expression dataset. In addition we used whole genome resequencing of the parental lines-two commonly used laboratory strains-to predict polymorphic transcription factor binding sites for SD. We integrated these data with previously published genomic datasets from expression microarrays and a modifier mutation screen. By searching for genes showing a congruent signal across multiple datasets, we were able to identify a robust set of candidate loci contributing to the background-dependent effects of mutations in sd. We also show that the majority of background-dependent modifiers previously reported are caused by higher-order epistasis, not quantitative noncomplementation. These findings provide a useful foundation for more detailed investigations of genetic background dependence in this system, and this approach is likely to prove useful in exploring the genetic basis of other traits as well.