Hanson R L, Ehm M G, Pettitt D J, Prochazka M, Thompson D B, Timberlake D, Foroud T, Kobes S, Baier L, Burns D K, Almasy L, Blangero J, Garvey W T, Bennett P H, Knowler W C
Phoenix epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
Am J Hum Genet. 1998 Oct;63(4):1130-8. doi: 10.1086/302061.
Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes 1q and 7q.
遗传因素影响II型糖尿病的发展,但最常见糖尿病类型的基因位点尚未确定。对皮马印第安人(一个II型糖尿病患病率很高的美国原住民群体)进行了基因组扫描,以确定与糖尿病和体重指数(BMI)相关的基因位点。在包含966名兄弟姐妹的264个核心家庭中,对516个常染色体标记进行了基因分型,相邻标记之间的中位距离为6.4厘摩。采用方差成分法来检验与年龄调整后的糖尿病评分以及BMI的连锁关系。在多点分析中,与年龄调整后的糖尿病连锁的最有力证据(LOD = 1.7)位于11号染色体q臂,该区域也与BMI关联最为紧密(LOD = 3.6)。双变量连锁分析强烈拒绝了与任一性状均无连锁以及该基因位点对两个性状之间的协变无贡献的零假设。同胞对分析表明在1号染色体和7号染色体q臂上存在其他潜在的糖尿病易感基因位点。