GENES FOR INSULIN-DEPENDENT DIABETES MELLITUS

胰岛素依赖型糖尿病的基因

• 批准号: 2414837
• 负责人: Richard S SPIELMAN
• 金额: $ 47.96万
• 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/2414837
• 关键词: British; chromosome 21; 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（IDDM）是一种严重的慢性疾病 胰岛细胞的自身免疫性破坏所致。 尽管遗传易感性一直受到高度关注 与 6p 染色体上的 HLA 系统相关，其他基因也 贡献。 我们建议协调一致地努力寻找所有 与 IDDM 易感性显着相关的基因；四 主要研究者将系统筛选的工作分工 带有 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 IDDM。 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或从两个大型存储库购买。 已有 300 多个 STRP 可用作标记，并且 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键入 家庭；然后将使用附加标记进行第二遍 给出l0cM的分辨率。 我们自己的实验室将筛选标记 映射到 6、13-19、21 和 22 号染色体；另一边的标记 常染色体将由本次其他两项资助的 PI 负责 合作：Graeme Bell（染色体 1-4 和 20）和 Patrick Concannon（5 号和 7-12 号染色体）。 来自所有三个实验室的数据将 发送给耶鲁大学的 Neil Risch 进行分析 以统一的方式收集整个标记。 当我们发现与某个标记的链接时，我们将使周围的标记饱和 带有附加标记的区域，以确认发现并携带 绘制出相关基因的更精细图谱。 如果已知基因位于 感兴趣的区域，他们将被筛选多态性或 可能与 IDDM 相关的突变。 此次活动的最终目的 研究的目的是表征赋予遗传因素 易感性，并使新的干预措施和治疗成为可能 IDDM。