title: High-resolution survey in familial Parkinson disease genes reveals multiple independent copy number variation events in PARK2.
abstract: A high density comparative genomic hybridization array was designed to evaluate CNVs in the genomic region of six familial PD genes in 181 PD cases and 67 controls. No CNV was found in PARK7, ATP13A2, PINK1, and LRRK2. Intronic-only CNVs were found in SNCA and PARK2 but were not associated with PD risk. A whole-gene duplication of SNCA was found in one case. The allele frequency of PARK2 exonic CNV is significantly higher in cases than in controls (P = 0.02), higher in early-onset (AAO ≤ 40) than in late-onset cases (P = 0.001), and higher in familial than in sporadic cases (P = 0.005). Except for single exon 2 duplications, all PARK2 exonic CNVs have different breakpoints, even when the same exon(s) were involved. In conclusion, except for SNCA and PARK2, CNVs are not a major contributing mechanism for the familial PD genes examined. The majority of PARK2 exonic CNVs are not recurrent.
authors.affiliation: John P Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors.forename: Liyong
authors.initials: L
authors.lastname: Wang
authors.forename: Karen
authors.initials: K
authors.lastname: Nuytemans
authors.forename: Guney
authors.initials: G
authors.lastname: Bademci
authors.forename: Cherylyn
authors.initials: C
authors.lastname: Jauregui
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Stephan
authors.initials: S
authors.lastname: Zuchner
mesh_terms: D017668:Age of Onset; D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: CGH; CNV; PARK2; Parkinson