Genetic Complexity and Parkinson's Disease

Author:

Scott William K.1,Stajich Jeffrey M.1,Yamaoka Larry H.1,Speer Marcy C.1,Vance Jeffery M.1,Roses Allen D.1,Pericak-Vance Margaret A.1,

Affiliation:

1. Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA;

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference32 articles.

1. Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

2. Golbe L. I., Di Iorio G., Bonavita V., Miller D. C., Duvoisin R. C., Ann. Neurol. 27, 276 (1990).

3. The families enrolled in this study were ascertained in the following manner. Each of the principal investigators of the 12 study sites identified idiopathic PD patients with one or more first-degree relatives with PD. All 94 families included in the analysis were responsive to levodopa. Specifically excluded were patients with a history of encephalitis neuroleptic therapy within the year before diagnosis evidence of normal pressure hydrocephalus or a clinical course with atypical features suggesting secondary Parkinsonism. All first-degree relatives of these patients who consented to participate in this study were subsequently examined and queried regarding the above exclusion criteria and atypical clinical features. Each of these individuals was assigned a status based on their history and the number of the following clinical signs that were present: resting tremor bradykinesia and rigidity. Individuals were coded as “affected” if their examination demonstrated at least two of the signs and had no other etiologies for parkinsonism or atypical clinical features “unclear” if they had only one sign but may have had a history of atypical clinical features and “at risk” if they had no signs. Mean age at onset of PD symptoms in affected individuals was 61.4 years (SD 13.1 years). Mean age at examination in affected individuals was 71.5 years (SD 10.2 years) and in unclear or at risk individuals was 68.4 years (SD 14.5 years).

4. Microsatellite markers spanning the region defined by Polymeropoulos et al. (1) were selected for the analysis; the resulting genetic map was: D4S2361-7.7cM-D4S2409-5.3cM-D4S2380-4cM-D4S1647-10.5cM-D4S2623 (Cooperative Human Linkage Center database is online at ). Two-point and multipoint lod scores were calculated with the use of the VITESSE software package [J. R. O'Connell and

5. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set–recoding and fuzzy inheritance

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