[Linkage disequilibrium between the Machado-Joseph disease and intragenic polymorphisms]

Machado-Joseph disease (MJD) is a progressive neurodegenerative disease which is characterized clinically by cerebellar ataxia and variable associated symptoms; it is inherited with an autosomal dominant manner. The disease is caused by an unstable expansion of the CAG repeat in MJD1 that maps to chromosome 14q32.1. There have been reported three intragenic polymorphic sites in MJD1. One is CA 926A/CAG within the CAG repeat, the others are accompanying with amino acid changes; 318Arg(987 CGG)/Gly(GGG) and 361Stop(TA1118A)/Tyr(TAC). Haplotype analyses showed 987C-1118A is exclusively associated with MJD chromosomes and normal chromosomes carrying the larger CAG repeat in the Japanese population. These results suggested that linkage disequilibrium between the MJD and intragenic polymorphisms, and the possibility of the presence of the haplotype which is prone to expansion of the CAG repeat.