Article

Complete Genomic Screen in Parkinson Disease

Center for Human Genetics, Box 3445, Duke University Medical Center, Durham, NC 27710, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 12/2001; 286(18):2239-44. DOI: 10.1001/jama.286.18.2239
Source: PubMed

ABSTRACT The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD.
To identify genetic risk factors for idiopathic PD.
Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status.
Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis.
Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients.
Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

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    • "Initially, we evaluated 396 unrelated cases with PD (non-Hispanic/Latino Caucasians, range of age-at-onset (AAO): 10–85 year, average AAO: 53.6 year) and 12 cases of essential tremor with Parkinsonism (ETP) (Rocca et al., 1998). Patients were collected by 1 of 13 ascertainment centres in the PD Genetics Collaboration (Scott et al., 2001) or by the Morris K. Udall Parkinson Disease Center of Excellence (PI: Vance JM) ascertainment core. These participants were recruited primarily by participating movement disorder and neurology clinics. "
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    • "The abundant expression of Fibroblast Growth Factor 20 (FGF20) in the midbrain, its role in dopaminergic (DA) neuron survival, and its location on chromosome 8 p22-p21.3 close to a Parkinson's disease (PD) linkage peak (Scott et al., 2001), have made FGF20 a promising candidate gene for PD. As a neurotrophin, FGF20 plays critical roles not only in the growth and survival of neurons in early development but also in the biology of adult neurons. "
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