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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。非胰岛素依赖型糖尿病(NIDDM)的显著遗传易感基因是由同卵双胞胎的高度一致性、强烈的家族聚集性以及来自疾病和中间表型的主基因分离分析的证据而提出的。尽管进行了广泛的研究，但还没有最终确定有易感的生化缺陷。已知的基因座可以解释1%的遗传性糖尿病。位置搜索策略为识别糖尿病易感基因和了解NIDDM病理生理学的早期阶段提供了一种强有力的替代方法。我们的数据驳斥了NIDDM代表高外显性单一同质性疾病的假设。这一建议是我们寻求NIDDM发病机制的重要遗传基础的合乎逻辑的演变，考虑到我们基因组筛选的结果，我们的系谱资源大大扩大，人类连锁和物理图谱方面的巨大进步，以及复杂疾病分析中不断演变的思想。我们假设NIDDM的易感性是由一个在少基因疾病模型中具有主要临床影响的基因决定的，该基因座将导致一个可识别的表型亚群，这些家系在65岁之前有强烈的NIDDM家族史。