Wang Susanna, Yehya Nadir, Schadt Eric E, Wang Hui, Drake Thomas A, Lusis Aldons J
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
PLoS Genet. 2006 Feb;2(2):e15. doi: 10.1371/journal.pgen.0020015. Epub 2006 Feb 3.
The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, "genetical genomic" analyses have not yet addressed the degree to which their conclusions are affected by sex. We constructed and densely genotyped a large F2 intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an apolipoprotein E null (ApoE-/-) background. This BXH.ApoE-/- population recapitulates several "metabolic syndrome" phenotypes. The cross consists of 334 animals of both sexes, allowing us to specifically test for the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significant proportion of which are sex-biased. We used these analyses to dissect the genetics of gonadal fat mass, a complex trait with sex-specific regulation. We present evidence for a remarkably high degree of sex-dependence on both the cis and trans regulation of gene expression. We demonstrate how these analyses can be applied to the study of the genetics underlying gonadal fat mass, a complex trait showing significantly female-biased heritability. These data have implications on the potential effects of sex on the genetic regulation of other complex traits.
将表达谱分析与连锁分析相结合，越来越多地用于鉴定复杂表型背后的基因。性别对许多生理特征调节的影响已有充分记录；然而，“遗传基因组”分析尚未探讨其结论受性别的影响程度。我们构建了一个大型F2杂交群体，并在载脂蛋白E基因敲除（ApoE-/-）背景下，对来自近交系小鼠C57BL/6J和C3H/HeJ的该群体进行了高密度基因分型。这个BXH.ApoE-/-群体再现了几种“代谢综合征”表型。该杂交群体由334只雌雄动物组成，使我们能够专门测试连锁对性别的依赖性。我们检测到数千个肝脏基因表达数量性状位点，其中很大一部分存在性别偏差。我们利用这些分析来剖析性腺脂肪量的遗传学，性腺脂肪量是一种具有性别特异性调节的复杂性状。我们提供的证据表明，基因表达的顺式和反式调节都高度依赖性别。我们展示了如何将这些分析应用于性腺脂肪量遗传学的研究，性腺脂肪量是一种具有明显女性偏向遗传力的复杂性状。这些数据对性别对其他复杂性状遗传调控的潜在影响具有启示意义。
