CHARACTERIZATION OF A MAJOR OBESITY LOCUS

描述(申请人提供)：肥胖症在美国正达到流行的程度，超过60%的美国人肥胖或超重。肥胖有很强的遗传成分，然而，关于影响肥胖的常见等位基因的具体身份，人们知之甚少。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。BC9-HG/HG小鼠在C57B6J-HG/HG背景上存在9号染色体CAST/EIJ等位基因。BC9-HG/HG雌性小鼠比对照组小鼠肥胖57%，雄性肥胖30%，HG是小鼠10号染色体上的一个缺失，导致体型增加30%-50%，证据表明BCQ-HG/HG小鼠肥胖需要HG。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，并将确定肥胖是否依赖于HG的存在。目的2利用同源F2群体来缩小携带肥胖QTL的基因组间隔。最后，Aim 3使用遗传基因组学方法来定位同源基因区间内的基因的eQTL。来自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.