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功能障碍在帕金森氏病（PD）的发病机理和病理生理学中的作用。现在已经确定了PD受试者中线粒体复合物I缺陷的存在。 这种缺陷似乎是由于线粒体DNA（mtDNA）异常而出现的，并且可以遗传或获得。核心的目的是支持四个针对以下方面的项目：1）在PD受试者和对照中对mtDNA进行测序； 2）表征PD中的线粒体结构和功能； 3）阐明PD的遗传病因； 4）阐明线粒体功能障碍与神经元死亡之间的关系。为此，核心由四个交互式和相互依存的组成组成：i）给药； ii）主题和确定性； iii）分子遗传学； iv）数据管理和生物统计学。管理组件（i）将监督中心的整个操作，并将服务于所有四个项目以及核心的平衡。核心的受试者和确定成分（II）将产生并完全表征PD的受试者。此核心功能对于所有四个项目都至关重要。多路复用家庭的确定将为项目1和3服务，而核心功能正在确定和验证受试者的家族史将直接服务于项目3，而其他项目则通过进一步表征其MTDNA可以纳入cybrids的受试者而间接地服务。分子遗传成分（III）将创建为项目1、2和4，在项目3中研究的项目1、2和4的囊肿，用于先前描述的与PD相关的核DNA突变，以及在所有受试者和对照方面的核心核和线粒体DNA。核心的数据管理和生物统计学组成部分（IV）将为所有四个项目提供服务；但是，特别是项目3提出了对性别对PD传播的影响的复杂隔离分析和其他统计遗传分析。