Pérusse Louis, Rankinen Tuomo, Zuberi Aamir, Chagnon Yvon C, Weisnagel S John, Argyropoulos George, Walts Brandon, Snyder Eric E, Bouchard Claude
Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Sainte-Foy, Québec, Canada.
Obes Res. 2005 Mar;13(3):381-490. doi: 10.1038/oby.2005.50.
This paper presents the eleventh update of the human obesity gene map, which incorporates published results up to the end of October 2004. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTLs) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2004, 173 human obesity cases due to single-gene mutations in 10 different genes have been reported, and 49 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 166 genes which, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 221. The number of human obesity QTLs derived from genome scans continues to grow, and we have now 204 QTLs for obesity-related phenotypes from 50 genome-wide scans. A total of 38 genomic regions harbor QTLs replicated among two to four studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably with 358 findings of positive associations with 113 candidate genes. Among them, 18 genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. Overall, >600 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful publications and genomic and other relevant sites can be found at http://obesitygene.pbrc.edu.
本文介绍了人类肥胖基因图谱的第十一次更新，其中纳入了截至2004年10月底的已发表研究结果。本文综述了来自单基因突变肥胖病例、表现为肥胖临床特征的孟德尔疾病、与肥胖相关的转基因和基因敲除小鼠模型、动物杂交实验的数量性状基因座（QTL）、候选基因关联研究以及基因组扫描连锁分析的证据。截至2004年10月，已报道了10种不同基因的单基因突变导致的173例人类肥胖病例，49个与人类肥胖相关的孟德尔综合征相关基因座已被定位到基因组区域，并且大多数这些综合征的致病基因或强候选基因已被确定。有166个基因，当在小鼠中发生突变或作为转基因表达时，会导致影响体重和肥胖的表型。目前动物模型报道的QTL数量达到221个。来自基因组扫描的人类肥胖QTL数量持续增加，目前我们有来自50次全基因组扫描的204个与肥胖相关表型的QTL。共有38个基因组区域含有在两到四项研究中重复的QTL。报告特定基因的DNA序列变异与肥胖表型之间关联的研究数量也大幅增加，有358项与113个候选基因的阳性关联研究结果。其中，18个基因得到至少五项阳性研究的支持。肥胖基因图谱显示了除Y染色体外所有染色体上的假定基因座。总体而言，超过600个基因、标记和染色体区域已与人类肥胖表型相关或连锁。该图谱电子版可在http://obesitygene.pbrc.edu上找到，其中包含与有用出版物以及基因组和其他相关网站的链接。
