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.
The American Journal of Human Genetics. 1998-10-01; 63(4): 1060-1066
DOI: 10.1086/302067
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1. Am J Hum Genet. 1998 Oct;63(4):1060-6.
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.
Takano H(1), Cancel G, Ikeuchi T, Lorenzetti D, Mawad R, Stevanin G, Didierjean
O, Dürr A, Oyake M, Shimohata T, Sasaki R, Koide R, Igarashi S, Hayashi S,
Takiyama Y, Nishizawa M, Tanaka H, Zoghbi H, Brice A, Tsuji S.
Author information:
(1)Department of Neurology, Brain Research Institute, Niigata University, Japan.
To test the hypothesis that the frequencies of normal alleles (ANs) with a
relatively large number of CAG repeats (large ANs) are related to the prevalences
of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph
disease), 6, and dentatorubral-pallidoluysian 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 individuals in each population. The relative prevalences of SCA1 and SCA2
were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than
in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation
that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2
(alleles >22 repeats) were significantly higher in Caucasians than in Japanese.
The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher
in Japanese pedigrees (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/SCA3 (>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 the dominant SCAs with the
distributions of large ANs strongly support the assumption that large ANs
contribute to generation of expanded alleles (AEs) and the relative prevalences
of the dominant SCAs.
DOI: 10.1086/302067
PMCID: PMC1377499
PMID: 9758625 [Indexed for MEDLINE]