MAPPING OF THE GENE FOR MACHADO-JOSEPH DISEASE WITHIN A 3.6-CM INTERVAL FLANKED BY D143291 D14S280 AND D14S81, ON THE BASIS OF STUDIES OF LINKAGE AND LINKAGE DISEQUILIBRIUM IN 24 JAPANESE FAMILIES/

The gene locus of Machado-Joseph disease (MJD) has recently been mappe d within a 29-cM subregion of 14q chromosome. We did a linkage study o f 24 multigenerational MJD Japanese pedigrees, in an attempt to narrow the candidate region of this gene. Pairwise and multipoint linkage an alysis, together with haplotype segregation analysis, led to the concl usion that the MJD gene is located at the 6.8-cM interval between D14S 256 and D14S81 (Z(max) = 24.78, multipoint linkage analysis). D14S291 and D14S280, located at the center of this interval, showed no obligat e recombination with the MJD gene (Z(max) = 5.93 for D14S291 and 9.99 for D14S280). A weak, but significant, linkage disequilibrium of MSD g ene was noted with D14S81 (P < .05) but not with D14S291 or D14S280. T hese results suggest that a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely location of the MJD gene and that it is closest to D14S81.