CHARACTERIZATION OF A MAJOR OBESITY LOCUS

描述（由申请人提供）：肥胖在美国已达到流行病的比例，超过60%的美国人肥胖或超重。肥胖具有很强的遗传成分，然而，关于具有影响肥胖的共同等位基因的基因的特定身份，相对知之甚少。为了表征影响肥胖的自然遗传变异，我建议研究BCQ-hg/hg同源株。BC 9-hg/hg小鼠在C57 B1/6 J-hg/hg背景上对于CAST/E1 J染色体9等位基因是同源的。BC 9-hg/hg雌性比对照小鼠肥胖57%，雄性比对照小鼠肥胖30%，hg是小鼠10号染色体上的缺失，导致体型增加30-50%，有证据表明，hg是BCQ-hg/hg小鼠肥胖所必需的。为了更好地理解BCQ-hg/hg肥胖的本质，我概述了三个具体目标。目的1测量年龄和饮食对BCQ-hg/hg肥胖的影响，并确定肥胖是否依赖于hg的存在。目的2使用同源衍生的F2群体来缩小携带肥胖QTL的基因组区间。最后，目标3使用遗传基因组学方法来定位同源区间内基因的eQTL。这些目标的数据将增强我们对肥胖的遗传学和生理学的理解。

DESCRIPTION (provided by applicant): Obesity is reaching epidemic proportions in the U.S. with over 60% of Americans being either obese or overweight. Obesity has a strong genetic component, however, relatively little is known regarding the specific identity of genes with common alleles influencing obesity. To characterize natural genetic variation influencing obesity I propose to study the BCQ-hg/hg congenic strain. BC9-hg/hg mice are congenic for CAST/EiJ chromosome 9 alleles on a C57B\/6J-hg/hg background. BC9-hg/hg females are 57% and males are 30% more obese than control mice, hg is a deletion on mouse chromosome 10 leading to a 30-50% increase in body size and evidence suggests that hg is required for obesity in BCQ-hg/hg mice. To better understand the nature of BCQ-hg/hg obesity I have outlined three specific aims. Aim 1 measures the effect of age and diet on BCQ-hg/hg obesity and will determine if obesity is dependent on the presence of hg. Aim 2 uses a congenic-derived F2 population to narrow the genomic interval harboring the obesity QTL. Lastly, aim 3 uses a genetical genomics approach to map eQTL for genes within the congenic interval. Data from these aims will enhance our understanding of the genetics and physiology of obesity.