GENETICS OF TYPE II DIABETES

II 型糖尿病的遗传学

• 批准号: 7377698
• 负责人: Steven C Elbein
• 金额: $ 0.96万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377698
• 关键词: GENETICS; TYPE; II; DIABETES

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A significant inherited susceptibility locus for non-insulin dependent diabetes (NIDDM) is suggested by a high concordance in identical twins, strong familial aggregation, and evidence from segregation analysis for a major gene for both the disease and intermediate phenotypes. Despite extensive study, no predisposing biochemical defect has been identified conclusively. Known loci explain <1% of inherited diabetes. The positional search strategy offers a powerful alternative approach to identify diabetes susceptibility genes and to understand the early stages of NIDDM pathophysiology. Our data reject the hypothesis that NIDDM represents a single homogeneous disease with high penetrance. This proposal is the logical evolution of our quest for an important genetic basis to NIDDM pathogenesis, given the results of our genome screen, our greatly expanded pedigree resource, the tremendous advances in both the human linkage and physical maps, and the evolving ideas in complex disease analysis. We hypothesize that NIDDM susceptibility is determined by a locus with major clinical impact in an oligogenic disease model, and that this locus will result in an identifiable phenotypic subgroup of pedigrees with a strong family history of NIDDM onset before age 65.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。非胰岛素依赖性糖尿病（NIDDM）的显着遗传易感性基因座是通过识别双胞胎的高一致性，强大的家族聚集以及隔离分析的证据来表明该疾病和中间表型的主要基因的证据。尽管进行了广泛的研究，但尚未确定易感生化缺陷。已知的基因座解释<1％的遗传糖尿病。位置搜索策略提供了一种强大的替代方法，可以识别糖尿病易感基因并了解NIDDM病理生理学的早期阶段。我们的数据拒绝了NIDDM代表具有高渗透率的单一同质疾病的假设。这项建议是我们寻求重要遗传基础对NIDDM发病机理的逻辑演变，鉴于我们的基因组筛查的结果，我们的谱系资源大大扩展，人类链接和物理图的巨大进步以及复杂疾病分析中不断发展的思想。我们假设NIDDM的敏感性取决于在寡原疾病模型中具有重大临床影响的基因座，并且该基因座将导致可识别的表型亚组，具有较强的NIDDM家族史在65岁之前的NIDDM发作。