title: Genomewide SNP assay reveals mutations underlying Parkinson disease.
abstract: Technologies that allow genotyping of more than 100,000 polymorphisms in a single assay enable the execution of genomewide SNP (GWSNP) association studies to identify common genetic variants underlying traits. Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the PARK2 locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within PARK2 were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease.
authors.affiliation: Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Simon-Sanchez
authors.forename: Sonja
authors.initials: S
authors.lastname: Scholz
authors.forename: Maria del Mar
authors.initials: Mdel M
authors.lastname: Matarin
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Dena
authors.initials: D
authors.lastname: Hernandez
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Angela
authors.initials: A
authors.lastname: Britton
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D015894:Genome, Human / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction