Genetic dissection of obesity in polygenic animal models.

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.