Xu W, Reed D R, Ding Y, Price R A
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA.
Obes Res. 1995 Nov;3(6):559-62. doi: 10.1002/j.1550-8528.1995.tb00190.x.
Mutant alleles of the agouti gene cause obesity in the mouse and the homologous gene in humans has been mapped to chromosome 20q11.2. An allelic variant of the agouti gene could account for obesity in humans and we tested this hypothesis by genotyping 210 sibling pairs from 45 families segregating an obesity phenotype. Using sibling pair linear regression analysis, evidence for linkage between obesity and markers flanking the agouti locus and other markers spanning chromosome 20q was assessed. We found no correlation between identity-by-descent at these markers and obesity differences within pairs. In the mouse, obesity caused by mutations of the agouti gene develops later in life, so a subset of families with adult-onset obesity were also tested for linkage, with negative results. Although it is not possible to exclude alleles of the agouti gene as a contributor to obesity in humans, the absence of positive linkage in this study suggests that either the agouti gene has small effects or the allele frequency is low.
刺鼠基因的突变等位基因会导致小鼠肥胖，人类中的同源基因已被定位于20号染色体长臂11区2带。刺鼠基因的一个等位基因变体可能是人类肥胖的原因，我们通过对来自45个分离肥胖表型的家庭的210对同胞进行基因分型来检验这一假设。使用同胞对线性回归分析，评估肥胖与刺鼠基因座侧翼标记以及跨越20号染色体长臂的其他标记之间的连锁证据。我们发现这些标记处的同源性与同胞对之间的肥胖差异没有相关性。在小鼠中，由刺鼠基因突变引起的肥胖在生命后期出现，因此还对一部分成年后发病的肥胖家庭进行了连锁测试，结果为阴性。虽然不能排除刺鼠基因的等位基因是人类肥胖的一个促成因素，但本研究中缺乏阳性连锁表明，要么刺鼠基因的影响很小，要么其等位基因频率很低。
