CORE--CLINICAL, MOLECULAR GENETICS & DATA MANAGEMENT

核心——临床、分子遗传学

• 批准号: 6618258
• 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/6618258
• 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体I功能障碍在帕金森病(PD)的发病机制和病理生理学中的作用。帕金森病患者中存在线粒体复合体I缺陷，这一点现已得到证实。这种缺陷似乎是线粒体DNA(MtDNA)异常的结果，可能是遗传的，也可能是后天获得的。CORE的目的是支持四个项目，旨在：1)对帕金森病患者和对照组的线粒体DNA进行测序；2)表征帕金森病患者的线粒体结构和功能；3)阐明帕金森病的遗传病因；以及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和相互依存的部分组成：一)管理；二)科目权责和确定；三)分子遗传学；四)数据管理和生物统计。行政部门(一)将监督中心的整个运作，并将为所有四个项目以及核心的其他部分提供服务。核心的科目应计和确定部分(二)将产生并充分描述帕金森病患者的特征。这一核心功能对所有四个项目都是必不可少的。多重家庭的确定将为项目1和项目3服务，而核心职能是确定和验证受试者的家族史将直接为项目3服务，通过进一步确定其mtDNA可能被合并到线虫中的受试者的特征，间接为其他项目服务。分子遗传部分(III)将创建胞质杂交，为项目1、2和4服务，筛选项目3中研究的受试者与先前描述的与帕金森病相关的核DNA突变，并将所有受试者和对照的核和线粒体DNA储存。核心的数据管理和生物统计部分(四)将为所有四个项目提供服务；特别是项目3，该项目建议对帕金森病传播的性别影响进行复杂的隔离分析和其他统计遗传分析。