PARKINSON DISEASE COLLABORATIVE STUDY OF GENETIC LINKAGE

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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.