GENETICS OF NON-INSULIN DEPENDENT DIABETES MELLITUS

非胰岛素依赖性糖尿病的遗传学

• 批准号: 6432203
• 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/6432203
• 关键词: Native Americans; child (0-11); clinical research; diabetes mellitus genetics; disease /disorder proneness /risk; family genetics; gene expression; genetic markers; genotype; human genetic material tag; human subject; linkage mapping; noninsulin dependent diabetes mellitus

Type 2 diabetes mellitus is a common chronic disease that develops in most populations in late 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 has been well-documented, and segregation analysis suggests the possibility of a single major gene affecting age of onset. Genetic determinants of type 2 diabetes mellitus, its risk factors and its complications 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 during the epidemiologic studies. An autosomal genome-wide linkage study, using 516 genetic markers, has been completed for 1338 individuals in 112pedigrees potentially informative for linkage studies of diabetes. The results of these analyses identified strong evidence for a gene influencing both obesity and diabetes on chromosome 11 and evidence for additional diabetes-susceptibility genes on chromosomes 1 and 7. In addition, potential genes influencing susceptibility to diabetic nephropathy were identified on chromosomes 7, and 18. Strong evidence for a locus on chromosome 19 influencing serum cholesterol concentrations was also found. Efforts at extending these findings through genotyping individuals in additional pedigrees and through fine-mapping are now underway. Methods to assess parent-of-origin effects in linkage analysis have also been developed.

2型糖尿病是一种常见的慢性疾病，在大多数中期人群中都会发展。亚利桑那州的皮马印第安人的这种疾病患病率很高，与许多人群相反，该疾病通常在早期出现。由于长期的流行病学研究，该疾病的家族性质已得到充分证明，并且隔离分析表明，单个主要基因影响发病的年龄。 2型糖尿病的遗传决定因素，其风险因素及其并发症正在使用遗传连锁分析技术寻求。淋巴细胞细胞系是通过信息丰富的血统建立的。 从流行病学研究期间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个个人，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11上都影响肥胖和糖尿病的基因的有力证据，并证明了染色体1和7上其他糖尿病 - 敏感性基因的额外糖尿病敏感性基因。此外，在染色体7和18的糖尿病上还鉴定了糖尿病肾病的潜在敏感性，也影响了染色体7和18的强大证据。 成立。 现在正在进行通过基因分型人在其他血统中和通过精细映射来扩展这些发现的努力。 还开发了评估链接分析中父母效应的方法。