STRONG LINKAGE DISEQUILIBRIUM AND HAPLOTYPE ANALYSIS IN JAPANESE PEDIGREES WITH MACHADO-JOSEPH DISEASE

To identify the markers tightly linked to Machado-Joseph. disease (MJD ) and to investigate whether a limited number of ancestral chromosomes are shared by Japanese MJD pedigrees, a detailed linkage analysis emp loying D14S55, D14S48, D14S67, D14S291, D14S280, AFM343vf1, D14S81, D1 4S265, D14S62, and D14S65 was performed. The results of multipoint lin kage analysis as well as detection of critical recombination events in dicate that the gene for MJD is localized in a 4-cM region between D14 S280-D14S81. We found strong linkage disequilibria at AFM343vf1 and D1 4S81, and association of a few common haplotypes with MJD. These resul ts indicate that there is an obvious founder effect in Japanese MJD an d suggest the possibility of the existence of predisposing haplotypes which are prone to expansions of CAG repeats. (C) 1996 Wiley-Liss, Inc .