title: Genetic variability in SNCA and Parkinson's disease.
abstract: Over the last decades, increasing knowledge about the genetic architecture of Parkinson's disease has provided novel insights into the pathogenesis of the disorder, generating hypotheses for further research. Characterizing the role of SNCA, encoding the α-synuclein protein, has been a particularly important aspect of this development. The identification of SNCA as the first gene implicated in monogenic parkinsonism led to the recognition of α-synuclein as a key protein in the pathogenesis and a major component of pathological hallmark lesions. An association between common variants in SNCA and risk of sporadic Parkinson's disease has been established through numerous studies. We review our current understanding of SNCA variability contributing to Parkinson's disease, highlighting the characterization of functionally relevant susceptibility alleles as a major future challenge. We argue that new strategies will be needed to pinpoint the variants that are ultimately responsible for the signals detected in association studies, where targeted resequencing may represent an attractive initial approach.
authors.affiliation: Department of Neurology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950, Nydalen, 0424 Oslo, Norway. lasse.pihlstrom@ous-hf.no
authors.forename: Lasse
authors.initials: L
authors.lastname: Pihlstrøm
authors.forename: Mathias
authors.initials: M
authors.lastname: Toft
mesh_terms: D017398:Alternative Splicing; D002874:Chromosome Mapping; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D051844:alpha-Synuclein