REFINEMENT OF THE GENE LOCUS FOR AUTOSOMAL RECESSIVE JUVENILE PARKINSONISM (AR-JP) ON CHROMOSOME 6Q25.2-27 AND IDENTIFICATION OF MARKERS EXHIBITING LINKAGE DISEQUILIBRIUM

Citation
M. Saito et al., REFINEMENT OF THE GENE LOCUS FOR AUTOSOMAL RECESSIVE JUVENILE PARKINSONISM (AR-JP) ON CHROMOSOME 6Q25.2-27 AND IDENTIFICATION OF MARKERS EXHIBITING LINKAGE DISEQUILIBRIUM, JOURNAL OF HUMAN GENETICS, 43(1), 1998, pp. 22-31
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
1434-5161
Volume
43
Issue
1
Year of publication
1998
Pages
22 - 31
Database
ISI
SICI code
1434-5161(1998)43:1<22:ROTGLF>2.0.ZU;2-9
Abstract
Autosomal recessive juvenile parkinsonism (AR-JP) (MIM 600116) is a he reditary neurodegenerative disorder characterized by levodopa-responsi ve parkinsonism with a mean age at onset of 23.2 years. We recently ma pped the AR-JP gene locus to a 17-cM interval on chromosome 6q25.2-27. To further narrow the candidate region of the AR-JP gene, we performe d detailed linkage analysis using densely placed genetic markers in th is region (D6S437, D6S1581, D6S1579, D6S305, D6S411, SOD2, D6S253, D6S 1599, D6S1719 and D6S264). Pairwise linkage analysis revealed the high est cumulative maximal lod score of 9.13 at D6S1579 (theta = 0.05), an d multipoint linkage analysis revealed the highest cumulative lod scor e of 12.4 at the locus 3 cM telomeric to D6S1599. Observation of oblig ate recombination events narrowed the candidate region to a 13-cM regi on between D6S1579 and D6S264. Furthermore, we identified two marker l oci, D6S1579 and D6S1599, which exhibit strong linkage disequilibrium with the AR-JP locus: chi(2) (2 x n table) = 84.22; P < 0.0001, chi(2) [likelihood-ratio test (LRT)] = 20.66; P < 0.0001, lambda = 0.40 and chi(2) (2 x n table) = 63.37; P < 0.0001, chi(2) (LRT) = 10.32; P < 0. 0001, lambda = 0.30, respectively. These results suggest that the cand idate region for the AR-JP gene is most likely located near the 4-cM r egion encompassing D6S1579 and D6S1599.