title: An approach to finding brain-situated mutations in sporadic Parkinson's disease.
abstract: Sporadic Parkinson's disease (PD) is thought to have a major genetic component, but the variants involved remain mostly unknown. One possible reason for the difficulty in finding mutations underlying PD is that rare predominantly brain-situated somatic mutations underlie the disease; these mutations would be missed by analysing blood DNA only. To test the feasibility of looking for somatic mutations in PD brain tissue, we compared copy number variants (CNVs) between 8 PD and 26 control brains using Affymetrix 6.0 arrays. The median number of CNVs per brain, and the overall proportion of amplifications and deletions, were similar in PD and control brains. In 7 of the 8 PD brains, however, a total of 45 CNVs were found that were not present in control brains. Twelve of these CNVs overlapped with one or more genes, some of which are involved in pathways suspected in the pathogenesis of PD, or are rare. This study shows that PD brain CNVs can be detected, and raises the possibility that brain-situated mutations could underlie some cases of PD. A method of undertaking a definitive study of brain somatic mutations in PD, using massively parallel sequencing and multiple tissues, is suggested.
authors.affiliation: Department of Pathology, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia. roger.pamphlett@sydney.edu.au
authors.forename: Roger
authors.initials: R
authors.lastname: Pamphlett
authors.forename: Julia M
authors.initials: JM
authors.lastname: Morahan
authors.forename: Natasha
authors.initials: N
authors.lastname: Luquin
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*