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