Quantitative trait loci for energy balance traits in an advanced intercross line derived from mice divergently selected for heat loss.

Obesity in human populations, currently a serious health concern, is considered to be the consequence of an energy imbalance in which more energy in calories is consumed than is expended. We used interval mapping techniques to investigate the genetic basis of a number of energy balance traits in an F11 advanced intercross population of mice created from an original intercross of lines selected for increased and decreased heat loss. We uncovered a total of 137 quantitative trait loci (QTLs) for these traits at 41 unique sites on 18 of the 20 chromosomes in the mouse genome, with X-linked QTLs being most prevalent. Two QTLs were found for the selection target of heat loss, one on distal chromosome 1 and another on proximal chromosome 2. The number of QTLs affecting the various traits generally was consistent with previous estimates of heritabilities in the same population, with the most found for two bone mineral traits and the least for feed intake and several body composition traits. QTLs were generally additive in their effects, and some, especially those affecting the body weight traits, were sex-specific. Pleiotropy was extensive within trait groups (body weights, adiposity and organ weight traits, bone traits) and especially between body composition traits adjusted and not adjusted for body weight at sacrifice. Nine QTLs were found for one or more of the adiposity traits, five of which appeared to be unique. The confidence intervals among all QTLs averaged 13.3 Mb, much smaller than usually observed in an F2 cross, and in some cases this allowed us to make reasonable inferences about candidate genes underlying these QTLs. This study combined QTL mapping with genetic parameter analysis in a large segregating population, and has advanced our understanding of the genetic architecture of complex traits related to obesity.

人类群体中的肥胖目前是一个严重的健康问题，被认为是能量失衡的结果，即摄入的卡路里能量多于消耗的能量。我们使用区间作图技术来研究一个F11代高级互交小鼠群体中一些能量平衡性状的遗传基础，该群体是由为增加和减少热损失而选择的品系最初杂交产生的。我们在小鼠基因组20条染色体中的18条的41个独特位点上，共发现了这些性状的137个数量性状位点（QTL），其中X连锁的QTL最为普遍。对于热损失这一选择目标发现了两个QTL，一个在1号染色体远端，另一个在2号染色体近端。影响各种性状的QTL数量通常与之前对同一群体遗传力的估计一致，在两种骨矿物质性状中发现的数量最多，在采食量和几种身体组成性状中发现的数量最少。QTL的作用通常是加性的，一些QTL，特别是那些影响体重性状的QTL，具有性别特异性。在性状组（体重、肥胖和器官重量性状、骨骼性状）内，尤其是在处死时经体重调整和未经体重调整的身体组成性状之间，多效性广泛存在。对于一种或多种肥胖性状发现了9个QTL，其中5个似乎是独特的。所有QTL之间的置信区间平均为13.3 Mb，比在F2杂交中通常观察到的要小得多，在某些情况下，这使我们能够对这些QTL背后的候选基因做出合理推断。这项研究在一个大的分离群体中将QTL作图与遗传参数分析相结合，增进了我们对与肥胖相关的复杂性状的遗传结构的理解。