CORE--CLINICAL, MOLECULAR GENETICS & DATA MANAGEMENT

核心——临床、分子遗传学

• 批准号: 6664104
• 负责人: GEORGE F WOOTEN
• 金额: $ 23.19万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6664104
• 关键词: Parkinson's disease; biomedical facility; data management; family genetics; gene mutation; genetic registry /resource /referral center; human genetic material tag; human subject; human tissue; hybrid cells; mitochondrial DNA; nervous system disorder diagnosis; postmortem; statistics /biometry

The main scientific theme of this Center is to elucidate the role of mitochondrial Complex I dysfunction in the pathogenesis and pathophysiology of Parkinson's disease (PD). The presence of a mitochondrial Complex I defect in subjects with PD is now well established. This defect appears to arise as a consequence of abnormalities in mitochondrial DNA (mtDNA) and may be either inherited or acquired. The purpose of the Core is to support four projects aimed at: 1) sequencing mtDNA in PD subjects and controls; 2) characterizing mitochondrial structure and function in PD; 3) clarifying the genetic etiology of PD; and 4) elucidating the relationship between mitochondrial dysfunction and neuronal death. To that end, the Core is composed of four interactive and interdependent components: I) Administration; II) Subject Accrual and Ascertainment; III) Molecular genetics; and IV) Data Management and Biostatistics. The Administration Component (I) will oversee the entire operation of the Center and will serve all four projects as well as the balance of the Core. The Subject Accrual and Ascertainment Component (II) of the Core will accrue and fully characterize subjects with PD. THIS Core function is essential for all four projects. The ascertainment of multiplex families will serve Projects 1 and 3, while the Core function is ascertaining and validating the family history of subjects will serve Project 3 directly and the other Projects indirectly by further characterizing the subjects whose mtDNA may be incorporated into cybrids. The Molecular Genetic Component (III) will create cybrids to serve Projects 1, 2, and 4, screen subjects studied in Project 3 for previously described nuclear DNA mutations associated with PD, and bank nuclear and mitochondrial DNA on all subjects and controls. The Data Management and Biostatistics Component (IV) of the Core will serve all four projects; but particularly Project 3 which proposes complex segregation analysis and other statistical genetic analyses of gender effects on transmission of PD.

该中心的主要科学主题是阐明线粒体复合物 I 功能障碍在帕金森病 (PD) 发病机制和病理生理学中的作用。现已明确，帕金森病患者存在线粒体复合物 I 缺陷。 这种缺陷似乎是线粒体 DNA (mtDNA) 异常的结果，可能是遗传性的，也可能是后天获得的。核心的目的是支持四个项目，旨在：1）对 PD 受试者和对照的 mtDNA 进行测序； 2) 表征PD中线粒体的结构和功能； 3）阐明PD的遗传病因； 4）阐明线粒体功能障碍和神经元死亡之间的关系。为此，核心由四个相互作用且相互依赖的部分组成： I) 管理； II) 主体应计和确定； III) 分子遗传学； IV) 数据管理和生物统计学。管理部分（I）将监督中心的整个运营，并为所有四个项目以及核心项目的其余部分提供服务。核心的受试者累积和确定部分 (II) 将累积并充分描述 PD 受试者的特征。这个核心功能对于所有四个项目都是必不可少的。多重家族的确定将服务于项目1和3，而核心功能是确定和验证受试者的家族史，将直接服务于项目3，并通过进一步表征其mtDNA可能被纳入cybrids的受试者间接服务于其他项目。分子遗传组件 (III) 将创建细胞杂种来服务项目 1、2 和 4，筛选项目 3 中研究的受试者是否存在先前描述的与 PD 相关的核 DNA 突变，并储存所有受试者和对照的核和线粒体 DNA。核心的数据管理和生物统计部分（IV）将为所有四个项目提供服务；但特别是项目 3，它提出了复杂的隔离分析和其他统计遗传分析，分析性别对 PD 传播的影响。