GENES FOR INSULIN-DEPENDENT DIABETES MELLITUS

胰岛素依赖型糖尿病的基因

• 批准号: 3248022
• 负责人: Richard S SPIELMAN
• 金额: $ 32.27万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3248022
• 关键词: British; diabetes mellitus genetics; family genetics; genetic markers; genetic polymorphism; human genetic material tag; human subject; insulin dependent diabetes mellitus; linkage mapping; polymerase chain reaction; questionnaires

Insulin-dependent diabetes mellitus (IDDM) is a serious chronic disease resulting from autoimmune destruction of the pancreatic islet cells. Although intense attention has been centered on genetic susceptibility associated with the HLA system on chromosome 6p, other genes also contribute. We propose a coordinated collaborative effort to find all the genes contributing significantly to IDDM susceptibility; four principal investigators will divide the work of systematically screening the human genome with DNA markers (simple tandem repeat polymorphisms, STRPs), and analyzing the results to find markers showing linkage with IDDM. DNA samples from more than 200 families with multiple IDDM siblings will be available from our own labs or purchased from two large repositories. More than 300 STRPs are already available to use as markers, and the number is growing rapidly. Markers spanning the genome at intervals of about 20% recombination will be typed in the first pass through the families; then a second pass will be carried out with additional markers to give a resolution of l0cM. Our own laboratory will screen markers mapping to chromosomes 6, 13-19, 21 and 22; markers on the other autosomes will be the responsibility of PIs of two other grants in this collaboration: Graeme Bell (chromosomes 1-4 and 20), and Patrick Concannon (chromosomes 5 and 7-12). Data from all three labs will be sent to Neil Risch at Yale where analyses will be carried out on the entire collection of markers in a uniform way. When we find linkage to some marker, we will saturate the surrounding region with additional markers, in order to confirm the finding and carry out finer mapping of the gene responsible. If known genes are located in the region of interest, they will be screened for polymorphisms or mutations that might be associated with IDDM. The ultimate goal of this research is to characterize the genetic elements that confer susceptibility, and make possible new interventions and treatments for IDDM.

胰岛素依赖型糖尿病是一种严重的慢性疾病 由胰岛细胞的自身免疫性破坏引起。 尽管人们对遗传易感性的关注一直集中在 与染色体6p上的HLA系统相关，其他基因也 贡献. 我们建议采取协调一致的合作努力， 显著影响IDDM易感性的基因; 4 主要研究者将系统地筛选 具有DNA标记的人类基因组（简单串联重复多态性， STRP），并分析结果以找到显示与 胰岛素依赖型糖尿病。 来自200多个有多个IDDM兄弟姐妹的家庭的DNA样本将 可以从我们自己的实验室获得，也可以从两个大型存储库购买。 已经有300多个STRP可用作标记， 数量正在迅速增长。 跨越基因组的标记间隔为 大约20%的重组将在第一次通过时被分型， 家庭;然后第二遍将进行额外的标记 分辨率为10厘米。 我们自己的实验室将筛选标记 定位于染色体6、13-19、21和22;另一个上的标记 常染色体将是其他两个赠款的PI的责任， 合作：格雷姆贝尔（染色体1-4和20），和帕特里克 Concannon（染色体5和7-12）。 所有三个实验室的数据将 发送给耶鲁大学的尼尔·里施，在那里， 以统一的方式收集整个标记。 当我们找到与某个标记的联系时，我们会把周围的 区域与额外的标记，以确认发现和携带 绘制出更精细的基因图谱。 如果已知基因位于 感兴趣的区域，将筛选它们的多态性，或 可能与IDDM相关的突变。 这最终的目的 研究的目的是描述遗传因素， 易感性，并使新的干预和治疗成为可能， 胰岛素依赖型糖尿病。