Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes

Parkinson's disease (PD) is a common neurodegenerative disorder with clinic al features of bradykinesia, rigidity, resting tremor and postural instabil ity resulting from the deficiency of dopamine in the nigrostriatal system. Previously we mapped a susceptibility gene for an autosomal dominant form o f PD to a 10.6 cM region of chromosome 2p (PARK3; OMIM 602404). A common ha plotype shared by two North American kindreds (Families B and C) genealogic ally traced to Southern Denmark and Northern Germany suggested a founder ef fect. Here we report progress in the refinement of the PARK3 locus and sequ ence analysis of candidate genes within the region. Members of families B a nd C were genotyped using polymorphic markers, reducing the minimum common haplotype to eight markers spanning a physical distance of 2.5 Mb. Analysis of 14 genes within the region did not reveal any potentially pathogenic mu tations segregating with the disease, implying that none of these genes are likely candidates for PARK3.