A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2–q13.1
Article first published online: 27 FEB 2002
Copyright © 2002 Wiley-Liss, Inc.
Annals of Neurology
Volume 51, Issue 3, pages 296–301, March 2002
How to Cite
Funayama, M., Hasegawa, K., Kowa, H., Saito, M., Tsuji, S. and Obata, F. (2002), A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2–q13.1. Ann Neurol., 51: 296–301. doi: 10.1002/ana.10113
- Issue published online: 28 FEB 2002
- Article first published online: 27 FEB 2002
- Manuscript Revised: 21 SEP 2001
- Manuscript Accepted: 21 SEP 2001
- Manuscript Received: 23 JUL 2001
- Japanese Ministry of Education, Culture, Sports, Science and Technology. Grant Numbers: 12031224, 12210131, 1267061 (to KH)
- Kitasato University Graduate School of Medical Sciences. Grant Number: 9802 (to FO)
We performed genomewide linkage analysis of a Japanese family with autosomal dominant parkinsonism, which exhibits clinical features compatible with those of common Parkinson's disease. Parametric two-point linkage analysis yielded a highest log odds (LOD) score of 4.32 at D12S345 (12p11.21). Parametric multipoint linkage analysis of the 13.6cM interval around this marker yielded LOD scores almost uniformly of >4.0 with a Zmax of 4.71 at D12S85 (12q12). Haplotype analysis detected two obligate recombination events at D12S1631 and D12S339 and defined the disease-associated haplotype in the 13.6cM interval in 12p11.2–q13.1. This haplotype was shared by all the patients and by some unaffected carriers, suggesting that disease penetration in this family is incomplete. This low penetrance suggests that environmental or other genetic factors modify expression of the disease. Nonparametric two-point and multipoint linkage analyses, which are penetrance-independent, yielded Zmax LOD scores of 14.2 and 24.9 at D12S345, respectively, strongly supporting the mapping of the parkinsonism locus in this family to 12p11.23–q13.11. This chromosome region is different from any known locus for hereditary parkinsonism, in keeping with the unique genetic features of the parkinsonism in this family. The nomenclature of PARK8 was assigned to the new locus.