Norman R A, Leibel R L, Chung W K, Power-Kehoe L, Chua S C, Knowler W C, Thompson D B, Bogardus C, Ravussin E
Clinical Diabetes and Nutrition Section, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016-5319, USA.
Diabetes. 1996 Sep;45(9):1229-32. doi: 10.2337/diab.45.9.1229.
The homologues of single genes that cause obesity in rodents are suggested as candidate genes for modulation of body composition in humans. Among these genes are the four mouse mutations-diabetes (db), obesity (ob), tubby (tub), and yellow agouti (Ay). Variation in the human counterparts to these genes (OB, DB, TUB, and ASP, respectively) may contribute to human obesity, which is thought to have a substantial genetic component. To initially assess the potential contribution of these genes to human obesity, we examined polymorphic DNA markers that, by virtue of syntenic relationships to appropriate regions of the mouse genome, should be closely linked to the human counterparts of these genes. Using combined data from 716 Pima Indians comprising 217 nuclear families, we have tested a number of polymorphic microsatellite markers (three at DB, two at OB, five at TUB, and three at ASP) for sib-pair linkage to BMI, percentage body fat, resting metabolic rate, 24-h energy expenditure, and 24-h respiratory quotient. No significant linkages were found in an analysis of all sibships or in an analysis restricted to discordant sib pairs.
导致啮齿动物肥胖的单个基因的同源基因被认为是调节人类身体组成的候选基因。这些基因包括四种小鼠突变基因——糖尿病（db）、肥胖（ob）、矮胖（tub）和黄刺鼠（Ay）。这些基因在人类中的对应基因（分别为OB、DB、TUB和ASP）的变异可能导致人类肥胖，而人类肥胖被认为具有很大的遗传成分。为了初步评估这些基因对人类肥胖的潜在贡献，我们检测了多态性DNA标记，这些标记由于与小鼠基因组的适当区域存在同线关系，应该与这些基因在人类中的对应基因紧密连锁。利用来自716名皮马印第安人（包括217个核心家庭）的综合数据，我们测试了一些多态性微卫星标记（DB处3个、OB处2个、TUB处5个、ASP处3个）与同胞对的BMI、体脂百分比、静息代谢率、24小时能量消耗和24小时呼吸商的连锁关系。在对所有同胞关系的分析或仅限于不一致同胞对的分析中均未发现显著的连锁关系。
