LINKAGE DISEQUILIBRIUM ANALYSIS IN MACHADO-JOSEPH DISEASE PATIENTS OFDIFFERENT ETHNIC-ORIGINS

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration originally described in families of Portuguese-Azorean an cestry. The hypothesis that its present world distribution could resul t from the spread of an original founder mutation has been raised. To test this possibility we have conducted a linkage disequilibrium study of markers segregating with the MJD1 locus in a total of 64 unrelated families of different geographical origins. Significant association w as detected between the MJD1 locus and marker alleles at loci D14S280, D14S1050 and D14S81. All affected individuals, except one Chinese fam ily, had allele 3 (237 bp) at D14S280. This finding is consistent with a founder effect in our MJD population. However, distinct haplotypes were observed in patients originating from the two Azorean islands sho wing the highest disease prevalence; therefore, the possible existence of more than one founder mutation can not be excluded with the marker s currently available.