IDENTIFICATION OF AN OBESITY QUANTITATIVE TRAIT LOCUS ON MOUSE-CHROMOSOME-2 AND EVIDENCE OF LINKAGE TO BODY-FAT AND INSULIN ON THE HUMAN HOMOLOGOUS REGION 20Q

Chromosomal synteny between the mouse model and humans was used to map a gene for the complex trait of obesity, Analysis of NZB/BINJ x SM/J intercross mice located a quantitative trait locus (QTL) for obesity o n distal mouse chromosome 2, in a region syntenic with a large region of human chromosome 20, showing linkage to percent body fat (likelihoo d of the odds [LOD] score 3.6) and fat mass (LOD score 4.3). The QTL w as confirmed in a congenic mouse strain. To test whether the QTL contr ibutes to human obesity, we studied linkage between markers located wi thin a 52-cM region extending from 20p12 to 20q13.3 and measures of ob esity in 650 French Canadian subjects from 152 pedigrees participating in the Quebec Family Study, Sib-pair analysis based on a maximum of 2 58 sib pairs revealed suggestive linkages between the percentage of bo dy fat (P < 0.004), body mass index (P < 0.008), and fasting insulin ( P < 0.0005) and a locus extending approximately from ADA (the adenosin e deaminase gene) to MC3R (the melanocortin 3 receptor gene), These da ta provide evidence that a locus on human chromosome 20q contributes t o body fat and insulin in a human population, and demonstrate the util ity of using interspecies syntenic relationships to find relevant dise ase loci in humans.