GENETICS OF NON-INSULIN DEPENDENT DIABETES MELLITUS

非胰岛素依赖性糖尿病的遗传学

• 批准号: 6289859
• 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/6289859
• 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 have been established. DNA is available from other families in nuclear pellets extracted from blood specimens obtained during the epidemiologic studies. Polymorphic probes are applied to the DNA from selected individuals to search for evidence of linkage of these markers with diabetes and its complications. A genetic linkage mapping study has been completed for 1338 individuals in 112 pedigrees potentially informative for linkage studies of diabetes. Genotypes for 516 autosomal genetic markers have been determined. 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. Efforts at extending these findings through genotyping individuals in additional pedigrees and through fine-mapping are now underway. The linkage study also provided evidence for a gene on chromosome 19 influencing serum cholesterol concentrations in the population. - Diabetes mellitus, genetics, nephropathy - Human Subjects

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。已经建立了淋巴细胞细胞系从信息丰富的血统中建立的。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。将多态性探针应用于选定个体的DNA，以寻找与糖尿病及其并发症联系在一起的证据。一项遗传连锁图研究的研究已经完成了112个谱系中的1338个个体，有可能提供有关糖尿病联系研究的信息。已经确定了516个常染色体遗传标记的基因型。这些分析的结果鉴定出有力的基因对染色体11的基因和糖尿病的影响，并证明了染色体1和7上的其他糖尿病 - 易感性基因。此外，通过在染色体7和18的过程中鉴定出对糖尿病性肾病的识别，并在这些疾病中鉴定出了这些疾病，并通过良好的良好和良好的良好的态度鉴定出对糖尿病性肾病的敏感性。现在正在进行。连锁研究还提供了关于染色体19影响血清胆固醇浓度的基因的证据。 - 糖尿病，遗传学，肾病 - 人类受试者