Genetics Of Type 2 Diabetes Mellitus

2 型糖尿病的遗传学

• 批准号: 6532208
• 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/6532208
• 关键词: Native Americans; cell line; child (0-11); chromosomes; clinical research; diabetes mellitus genetics; diabetic nephropathy; disease /disorder proneness /risk; epidemiology; family genetics; gene expression; genetic markers; genetic susceptibility; genotype; human birth weight; human genetic material tag; human subject; insulin; linkage disequilibriums; linkage mapping; noninsulin dependent diabetes mellitus; obesity; pancreatic islet function; technology /technique development

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 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. An autosomal genome-wide linkage study, using 516 genetic markers, has been completed for 1338 individuals in 112 pedigrees potentially informative for linkage studies of diabetes. The results of these analyses 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 these loci using analysis of linkage disequilibrium are currently underway. In addition, techniques to assess parent-of-origin effects in linkage analysis have been developed and applied to the genome-wide linkage study. These analyses found little evidence that parent-of-origin effects are important for loci influencing susceptibility to diabetes or obesity, but strong evidence for a paternally-expressed locus influencing birth weight was found on chromosome 11p.

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。使用遗传连锁分析技术寻求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。使用516个遗传标记的常染色体全基因组连锁研究已经完成了1338个个体的112个谱系中的1338个个体，可能有可能提供有关糖尿病联系研究的信息。这些分析的结果确定了在染色体11q上影响肥胖和糖尿病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。目前正在使用链接不平衡分析来识别这些基因座的努力。此外，在链接分析中评估父母效应的技术已开发并应用于全基因组链接研究。这些分析几乎没有证据表明，父母的产生作用对于影响对糖尿病或肥胖症的易感性的基因座很重要，但是在11p染色体上发现了影响生育体重的遗传表达的基因座的有力证据。