[Linkage study of Machado-Joseph disease: genetic evidence for the locus different from SCA1]

Spinocerebellar ataxia 1 (SCA1) is the locus symbol of hereditary olivopontocerebellar atrophy, and it is mapped on the short arm of chromosome 6. D6S89 is the polymorphic DNA marker linked tightly to SCA1. In order to examine whether SCA1 and Machado-Joseph disease (MJD) loci are different from each other, we performed linkage study for D6S89 to MJD locus. A total of 20 pedigrees of MJD were analysed. Number of individuals consists of 211 members. Among them, 74 were affected. Consequently, 14 pedigrees showed negative lod score, and 6 showed weak positive lod scores at most of recombination fractions. As a whole, linkage between MJD locus and D6S89 was excluded at recombination fraction of 0.15. Our results further support the concept that MJD is not an allelic disorder but distinct genetic entity from SCA1.