Traits related to energy balance and obesity are exceptionally complex, with varying contributions of genetic susceptibility and interacting environmental factors. The use of mouse models has been a powerful driving force in understanding the genetic architecture of polygenic traits such as obesity. However, the use of mouse models for analysis of complex traits is at an important crossroad. Genome-wide association studies in humans are now leading to direct identification of obesity genes. In this review, we focus on three areas representing the current and future roles of mouse models regarding genetics of complex obesity. First, we summarize increasingly powerful ways to harness the strength of mouse models for discovery of genes affecting polygenic obesity. Second, we examine the status of using a systems biology approach to dissect the genetic architecture of obesity. And third, we explore the effects of recent findings indicating increasing levels of complexity in the nature of variation underlying, and the heritability of, complex traits such as obesity.

译文

:与能量平衡和肥胖有关的性状异常复杂,遗传易感性和相互作用的环境因素的贡献各不相同。鼠标模型的使用已成为了解肥胖等多基因性状遗传结构的强大动力。但是,使用鼠标模型分析复杂性状正处于重要的十字路口。人类的全基因组关联研究现在正导致肥胖基因的直接鉴定。在这篇综述中,我们集中在三个方面,它们代表了关于复杂肥胖症遗传学的小鼠模型的当前和未来作用。首先,我们总结了越来越强大的方法来利用小鼠模型的力量来发现影响多基因肥胖的基因。其次,我们研究了使用系统生物学方法剖析肥胖症遗传结构的现状。第三,我们探索了最近发现的影响,这些结果表明,潜在的变异性及其复杂性(如肥胖症)的遗传性的复杂性水平不断提高。

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