PARKINSON DISEASE COLLABORATIVE STUDY OF GENETIC LINKAGE

帕金森病是一种成人发病的神经退行性疾病 特征为运动迟缓、肌肉僵硬、静止性震颤和 姿势不稳 我们试图找出基因， 个人发展PD。具体而言，我们将： 1)确定并招募至少400对患有PD的兄弟姐妹。 2)收集资料包括：家谱资料;病历资料; 临床和流行病学数据。 3)采集血样用于基因组和线粒体DNA提取。 4)使用大约350个高度同源的基因组完成10 cM人类基因组筛选。 多态性微卫星重复标记。 5)进行连锁分析，以确定可能 携带PD基因。 6)对样本临床和流行病学变量进行分层， 提高识别PD基因座的能力。 7)分析受影响个体的线粒体DNA 突变。 我们的大样本将使我们能够成功地识别 使个体易患PD的基因。 最近一 4号染色体上的α-突触核蛋白基因的突变被报道在 四个常染色体显性PD家族;然而，其他研究 常染色体显性遗传的家庭和受影响的兄弟姐妹对的样本， 未证实4号染色体病因 此外，由于所有 必须在独立样本中重复显著的连锁结果 为了确保其有效性，本研究将提供手段， 重复其他研究的关联发现。 为了实现这些具体目标，与四个 核心组成部分已经建立：1）行政/联系分析 核心由印第安纳州的P. Michael Conneally博士指导 2）临床核心由Jean Hubble，M.D.指导。在俄亥俄州 帕金森研究小组（PSG），一个大型的， 北美临床研究者学术合作; 3） 基因分型实验室核心由威廉尼科尔斯，博士在 密歇根大学;和4）线粒体DNA核心由 埃默里大学的道格拉斯华莱士博士将分析 线粒体DNA

Parkinson Disease is an adult onset, neurodegenerative disease characterized by bradykinesia, muscular rigidity, resting tremor and postural instability. We seek to identify the gene(s) which predispose individuals to develop PD. Specifically, we will: 1) Identify and recruit a minimum of 400 sibling pairs with PD. 2) Collect data including: pedigree information; medical records; clinical and epidemiological data. 3) Collect blood samples for genomic and mitochondrial DNA extraction. 4) Complete a 10 cM human genome screen using approximately 350 highly polymorphic microsatellite repeat markers. 5) Perform linkage analysis to identify candidate regions likely to harbor PD gene(s). 6) Stratify the sample clinical and epidemiological variables to increase the power to identify PD loci. 7) Analyze mitochondrial DNA from affected individuals for mtDNA mutations. The large size of our sample will allow us to successfully identify the gene(s) which predispose an individual to develop PD. Recently a mutation in the alpha-synuclein gene on chromosome 4 was reported in four autosomal dominant PD families; however, studies in additional autosomal dominant families and a sample of affected sibling pairs have not confirmed a chromosome 4 etiology. In addition, since all significant linkage results must be replicated in independent samples in order to assure their validity, this study will provide the means to replicate linkage findings from other studies. In order to accomplish these specific aims a collaboration with four core components has been established: 1) Administrative/Linkage Analysis Core under the direction of P. Michael Conneally, Ph.D at Indiana University; 2) Clinical Core directed by Jean Hubble, M.D. at Ohio State University and comprised of the Parkinson Study Group (PSG), a large, North American academic collaboration of clinical investigators; 3) Genotyping Laboratory Core directed by William Nichols, Ph.D at the University of Michigan; and 4) Mitochondrial DNA core directed by Douglas Wallace, Ph.D at Emory University, who will analyze mitochondrial DNA.