PARKINSON DISEASE COLLABORATIVE STUDY OF GENETIC LINKAGE

帕金森病是一种成人起病的神经退行性疾病 以运动迟缓、肌肉僵硬、静止性震颤和 姿势不稳。我们试图找出易感基因(S) 个体发展为帕金森病。具体来说，我们会： 1)确定和招募至少400对有帕金森病的兄弟姐妹。 2)收集数据，包括：谱系信息、病历； 临床和流行病学资料。 3)采集血样进行基因组和线粒体DNA提取。 4)完成10厘米的人类基因组筛查，使用大约350个高度 多态微卫星重复标记。 5)进行连锁分析，以确定可能 港湾PD基因(S)。 6)对样本临床和流行病学变量进行分层，以 增加识别PD基因座的能力。 7)分析患者线粒体DNA中的mtDNA 突变。 我们的大样本将使我们能够成功地识别 易患帕金森病的基因(S)。最近一次 年报道了4号染色体上α-突触核蛋白基因的突变。 四个常染色体显性遗传性帕金森病家系；然而，在其他研究中 常染色体显性遗传家系和受影响的同胞对样本 没有确认4号染色体的病因学。此外，由于所有 显著的连锁结果必须在独立样本中重复 为了确保它们的有效性，本研究将提供以下方法 重复其他研究中的关联发现。 为了实现这些具体目标，与四个国家合作 已建立核心组件：1)管理/链接分析 在P.Michael Conneally的指导下，印第安纳州的博士 大学；2)俄亥俄州立大学医学博士Jean Hubble指导的临床核心 并由帕金森研究小组(PSG)组成，这是一个大型的， 北美临床研究人员学术合作；3) 基因分型实验室核心，由威廉·尼科尔斯指导，博士在 密歇根大学；以及4)由 道格拉斯·华莱士，埃默里大学博士，他将分析 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.