CLOSE ASSOCIATIONS BETWEEN PREVALENCES OF DOMINANTLY INHERITED SPINOCEREBELLAR ATAXIAS WITH CAG-REPEAT EXPANSIONS AND FREQUENCIES OF LARGE NORMAL CAG ALLELES IN JAPANESE AND CAUCASIAN POPULATIONS

To test the hypothesis that the frequencies of normal alleles (ANs) wi th a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA ty pes 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluys ian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal in dividuals in each population. The relative prevalences of SCA1 and SCA 2 were significantly higher in Caucasian pedigrees (15% and 14%, respe ctively) than in Japanese pedigrees (3% and 5%, respectively), corresp onding to the observation that the frequencies of large ANs of SCA1 (a lleles >30 repeats) and of SCA2 (alleles >22 repeats) were significant ly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigr ees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30% , 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCAS (>27 repeats), SCA6 (>13 repeats ), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of t he dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded all eles (AEs) and the relative prevalences of the dominant SCAs.