CORE--CLINICAL, MOLECULAR GENETICS & DATA MANAGEMENT

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。目前已充分证实PD受试者存在线粒体复合物I缺陷。 这种缺陷似乎是由于线粒体DNA（mtDNA）异常而引起的，可能是遗传的或后天获得的。该核心的目的是支持四个项目，旨在：1）测序PD受试者和对照组的mtDNA; 2）表征PD中的线粒体结构和功能; 3）阐明PD的遗传病因学; 4）阐明线粒体功能障碍与神经元死亡之间的关系。为此，核心由四个相互作用和相互依赖的组成部分组成：I）管理; II）受试者累积和确定; III）分子遗传学; IV）数据管理和生物统计学。行政部分（I）将监督中心的整个运作，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）将累积并充分表征PD受试者。这一核心职能对所有四个项目都至关重要。多重家族的确定将服务于项目1和项目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，其他项目通过进一步表征其mtDNA可能被整合到胞质杂种中的受试者来间接服务。分子遗传组件（III）将创建cybrids以服务于项目1，2和4，筛选项目3中研究的受试者先前描述的与PD相关的核DNA突变，并将所有受试者和对照组的核和线粒体DNA库。核心项目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，该项目提出了复杂的隔离分析和性别对PD传播影响的其他统计遗传分析。

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.