Faculty of Life Sciences, University of Manchester, Manchester M139PT, UK.
Mamm Genome. 2009 Sep-Oct;20(9-10):681-98. doi: 10.1007/s00335-009-9209-2. Epub 2009 Aug 6.
Genomic imprinting, where the effects of alleles depend on their parent-of-origin, can be an important component of the genetic architecture of complex traits. Although there has been a rapidly increasing number of studies of genetic architecture that have examined imprinting effects, none have examined whether imprinting effects depend on genetic background. Such effects are critical for the evolution of genomic imprinting because they allow the imprinting state of a locus to evolve as a function of genetic background. Here we develop a two-locus model of epistasis that includes epistatic interactions involving imprinting effects and apply this model to scan the mouse genome for loci that modulate the imprinting effects of quantitative trait loci (QTL). The inclusion of imprinting leads to nine orthogonal forms of epistasis, five of which do not appear in the usual two-locus decomposition of epistasis. Each form represents a change in the imprinting status of one locus across different classes of genotypes at the other locus. Our genome scan identified two different locus pairs that show complex patterns of epistasis, where the imprinting effect at one locus changes across genetic backgrounds at the other locus. Thus, our model provides a framework for the detection of genetic background-dependent imprinting effects that should provide insights into the background dependence and evolution of genomic imprinting. Our application of the model to a genome scan supports this assertion by identifying pairs of loci that show reciprocal changes in their imprinting status as the background provided by the other locus changes.
基因组印迹是指等位基因的效应取决于其亲源来源，它可以成为复杂性状遗传结构的重要组成部分。尽管已经有越来越多的研究探讨了遗传结构中的印迹效应，但没有研究检查印迹效应是否取决于遗传背景。这些效应对于基因组印迹的进化至关重要，因为它们允许一个基因座的印迹状态随着遗传背景的变化而进化。在这里，我们开发了一个包含印迹效应的上位性的两基因座模型，并将该模型应用于扫描小鼠基因组，以寻找调节数量性状基因座（QTL）印迹效应的基因座。包含印迹效应导致了九种正交形式的上位性，其中五种形式在上位性的通常两基因座分解中不存在。每种形式代表一个基因座在另一个基因座的不同基因型类别中的印迹状态的变化。我们的基因组扫描确定了两个不同的基因座对，它们显示出复杂的上位性模式，其中一个基因座的印迹效应在另一个基因座的遗传背景中发生变化。因此，我们的模型为检测遗传背景依赖性印迹效应提供了一个框架，这应该为基因组印迹的背景依赖性和进化提供深入的了解。我们将该模型应用于基因组扫描，通过识别在另一个基因座提供的背景发生变化时其印迹状态发生相互变化的基因座对，支持了这一说法。
