title: Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls.
abstract: Mutation of LRRK2, encoding dardarin, is the most common known genetic cause of Parkinson's disease (PD). The large size of this gene and the relative ease with which the most common mutations can be screened means that although more than 50 LRRK2 screening papers have been published, few have analyzed the entire coding sequence. Furthermore, no comprehensive sequence-based analysis has been performed on control samples. Here, we present sequencing of all coding exons in a series of 275 PD cases and 275 neurologically normal controls and analysis of the LRRK2 locus for whole gene multiplications or deletions. We also present case-control SNP association results using 74 SNPs genotyped across LRRK2. We identified six novel disease-associated missense mutations, including two that altered the same residue of the protein. These data and analysis of previously reported disease-segregating mutations shows that the majority of disease-causing mutations lie in the C-terminal half of the protein.
authors.affiliation: Molecular Genetics Unit, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. C.Paisan-Ruiz@ion.ucl.ac.uk
authors.forename: Coro
authors.initials: C
authors.lastname: Paisán-Ruíz
authors.forename: Priti
authors.initials: P
authors.lastname: Nath
authors.forename: Nicole
authors.initials: N
authors.lastname: Washecka
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005091:Exons; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*
chemical_list: D004247:DNA; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases