Pomp D
Department of Animal Science, University of Nebraska, Lincoln 68583, USA.
Behav Genet. 1997 Jul;27(4):285-306. doi: 10.1023/a:1025631813018.
In contrast to diseases caused by single-gene defects, many of the most common human maladies such as obesity, atherosclerosis, diabetes, and hypertension exhibit continuous phenotypic variation and a predominantly multifactorial and polygenic basis. Genes with roles in energy balance, nutrient partitioning, lipid and insulin metabolism, and a variety of behavioral traits are likely interacting with environmental stimuli to regulate obesity phenotypes. With the current proliferation of highly polymorphic genetic markers and the refinement of experimental approaches, it is now possible to screen thoroughly the genomes of model organisms for the individual genes or quantitative trait loci (QTL) that control measurable polygenic traits such as obesity. With the growing wealth of comparative mapping, it will be possible to predict the location of a homologous locus in the human after first mapping it in the mouse. Many experiments have been conducted in mice, rats, and pigs to estimate the number, location, and effect of QTL controlling obesity and related traits. This review describes the design and strategies of such studies and summarizes the results and their implications toward understanding the complex nature of obesity in humans.
与单基因缺陷引起的疾病不同，许多最常见的人类疾病，如肥胖、动脉粥样硬化、糖尿病和高血压，表现出连续的表型变异，且主要基于多因素和多基因。在能量平衡、营养分配、脂质和胰岛素代谢以及各种行为特征中起作用的基因可能与环境刺激相互作用，以调节肥胖表型。随着当前高多态性遗传标记的激增和实验方法的改进，现在有可能在模式生物的基因组中全面筛选控制肥胖等可测量多基因性状的单个基因或数量性状位点（QTL）。随着比较图谱的日益丰富，在小鼠中首次定位同源基因座后，将有可能预测其在人类中的位置。已经在小鼠、大鼠和猪身上进行了许多实验，以估计控制肥胖及相关性状的QTL的数量、位置和作用。本综述描述了此类研究的设计和策略，并总结了结果及其对理解人类肥胖复杂本质的意义。
