MOLECULAR GENETIC STUDIES OF ALZHEIMERS DISEASE

阿尔茨海默病的分子遗传学研究

• 批准号: 2250333
• 负责人: MARILYN S. ALBERT
• 金额: $ 32.02万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2250333
• 关键词: Alzheimer's disease; alleles; amyloid proteins; artificial chromosomes; chromosome 21; computer data analysis; computer program /software; computer simulation; cooperative study; family genetics; gene mutation; genetic mapping; genetic markers; genetic polymorphism; genetic techniques; genotype; human genetic material tag; human tissue; linkage mapping; nucleic acid sequence; polymerase chain reaction; protooncogene; siblings; statistics /biometry; stress proteins

This application is a response to RFA MH-92-15 pertaining to a 'Phase Two Cooperative Agreement for Genetic Studies Of Alzheimer's Disease' (AD). During Phase l, known as 'Diagnostic Centers for Psychiatric Linkage Studies', three research centers were funded to collect siblings pairs with AD. These investigators (from Harvard Medical School, Johns Hopkins Medical School and the University of Alabama), together with NIMH staff, have designed and implemented a common protocol whose goal is to collect a total of 400 sibling pairs with AD. This work is ongoing; to date, over 160 sibling pairs have been collected. During Phase 2, the three centers will continue to work together to identify the genes involved in AD, We plan to: l) Genotype sib-pairs and FAD pedigrees for polymorphic :markers spanning the human genome. 2) Assess affected members of the sib-pairs and FAD families for the presence of the three known mutations in the amyloid B protein precursor gene on chromosome 21 and other new ones which may arise in the course of the proposed studies. 3) Perform statistical analyses on the genotypic data as well as computer simulations to determine the best analytic strategy that should be employed to detect linkage, given genetic heterogeneity and the structures of the families being collected. 4) Type additional highly polymorphic markers in the relevant chromosomal region, once linkage has been found, to better define the region in which linkage has been found. 5) Maintain data in a computer database, with a common format across sites.

该应用是对RFA MH-92-15的响应 关于阿尔茨海默氏病遗传研究的合作协议”（AD）。 在L阶段，被称为“精神病联系的诊断中心” 研究”，三个研究中心被资助以收集兄弟姐妹对 与广告。这些调查人员（来自哈佛医学院，约翰·霍普金斯 医学院和阿拉巴马大学）与NIMH员工一起 已经设计和实施了一个共同的协议，其目标是收集 总共有400个兄弟姐妹对AD。 这项工作正在进行中；迄今为止，结束 收集了160对兄弟姐妹。 在第2阶段，这三个中心将继续共同努力 识别AD中涉及的基因，我们计划：l）基因型SIB对，并且 多态的FAD血统：跨越人类基因组的标记。 2） 评估SIB对的受影响成员和FAD家族的存在 在淀粉样B蛋白前体基因上的三个已知突变中 21号染色体和其他新的染色体可能在 拟议的研究。 3）对基因型数据进行统计分析 以及计算机模拟以确定最佳分析策略 应采用遗传异质性和 收集家庭的结构。 4）高度键入 一旦连接具有相关染色体区域的多态标记 找到了可以更好地定义找到链接的区域。 5）在计算机数据库中维护数据，并具有跨越的格式 站点。