Genetics Of Type 2 Diabetes Mellitus

2 型糖尿病的遗传学

• 批准号: 7153441
• 负责人: WILLIAM C KNOWLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7153441
• 关键词: Native Americans; adolescence (12-20); biotechnology; cell line; child (0-11); diabetes mellitus genetics; diabetes risk; disease /disorder onset; family genetics; gene expression; genetic markers; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; insulin; linkage disequilibriums; linkage mapping; noninsulin dependent diabetes mellitus; pancreatic islet function; patient oriented research; statistics /biometry

Type 2 diabetes mellitus is a common chronic disease that develops in most populations late in middle age. The Pima Indians of Arizona have a very high prevalence of this disease and, in contrast to many populations, the disease often presents at an earlier age. As a result of the long-term epidemiologic studies, the familial nature of the disease is well-documented, and segregation analysis suggests that genetic determinants may influence age of onset. Genetic determinants of type 2 diabetes mellitus and its risk factors are being sought using techniques of genetic linkage and association analysis. Lymphoblast cell lines have been established from informative pedigrees. DNA is available from other families in nuclear pellets extracted from blood specimens obtained in the epidemiologic studies and is amplified by whole genome amplification when needed. An autosomal genome-wide linkage study identified strong evidence for a locus influencing both obesity and diabetes on chromosome 11q. Evidence for an additional locus influencing diabetes and insulin secretory function was found on chromosome 1q. Efforts to identify the causative polymorphism or polymorphisms in both of these regions are currently underway using both a systematic analysis of linkage disequilibrium and analyses of candidate genes. Methods for statistical analyses of these studies are also being developed and evaluated. Several regions that appear to be in linkage disequilibrium with obesity-susceptibility alleles on chromosome 11 have been identified and several candidate genes have been analyzed. In collaboration with the Sanger Centre a dense (5 kb) linkage disequilibrium map of chromosome 1q is being generated for Pimas and for several other populations that have shown linkage to this region. Genotypes are being determined for a genome-wide association study of young-onset type 2 diabetes.

2型糖尿病是一种常见的慢性疾病，在中年后期大多数人群中发展。亚利桑那州的皮马印第安人的这种疾病患病率很高，与许多人群相比，该疾病通常在早期出现。由于长期的流行病学研究，该疾病的家族性是有据可查的，并且隔离分析表明遗传决定因素可能会影响发作年龄。使用遗传联系和关联分析技术寻求2型糖尿病及其危险因素的遗传决定因素。淋巴细胞细胞系是通过信息丰富的血统建立的。从流行病学研究中获得的血液标本中提取的核颗粒中，其他家族可从其他家族中获得DNA，并在需要时通过整个基因组扩增进行扩增。一项全染色体基因组连接研究确定了影响肥胖症和糖尿病11q染色体的基因座的有力证据。在1q染色体上发现了影响糖尿病和胰岛素分泌功能的其他基因座的证据。目前正在使用对链接不平衡的系统分析和候选基因分析的系统分析来确定这两个区域的致病多态性或多态性的努力。这些研究的统计分析方法也正在开发和评估。似乎已经鉴定出了第11个染色体上的肥胖症等位基因的几个区域，并且已经鉴定出了肥胖的敏感性等位基因，并且已经分析了几个候选基因。与Sanger中心合作，正在为PIMAS和其他几个与该区域链接的人群生成1Q染色体1Q的密集（5 kb）连锁图。正在确定针对全基因组2型糖尿病的全基因组关联研究的基因型。