Pomp Daniel, Nehrenberg Derrick, Estrada-Smith Daria
Department of Nutrition, Carolina Center for Genome Science, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Annu Rev Nutr. 2008;28:331-45. doi: 10.1146/annurev.nutr.27.061406.093552.
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.
与能量平衡和肥胖相关的性状极其复杂，遗传易感性和相互作用的环境因素的贡献各不相同。小鼠模型的使用在理解肥胖等多基因性状的遗传结构方面一直是一股强大的推动力。然而，使用小鼠模型分析复杂性状正处于一个重要的十字路口。目前人类全基因组关联研究正在直接鉴定肥胖基因。在这篇综述中，我们关注代表小鼠模型在复杂肥胖遗传学方面当前和未来作用的三个领域。首先，我们总结利用小鼠模型的优势来发现影响多基因肥胖的基因的越来越强大的方法。其次，我们研究使用系统生物学方法剖析肥胖遗传结构的现状。第三，我们探讨最近的研究结果所产生的影响，这些结果表明肥胖等复杂性状的潜在变异本质和遗传力的复杂性在不断增加。
