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.
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.
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DOI：
10.1086/302067
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发表时间：
1998-10
影响因子：
9.8
通讯作者：
H. Takano;G. Cancel;T. Ikeuchi;D. Lorenzetti;R. Mawad;G. Stevanin;O. Didierjean;A. Durr;M. Oyake;T. Shimohata;R. Sasaki;R. Koide;S. Igarashi;Shigenobu Hayashi;Y. Takiyama;M. Nishizawa;Hirosato Tanaka;H. Zoghbi;A. Brice;S. Tsuji
中科院分区：
文献类型：
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作者：
H. Takano;G. Cancel;T. Ikeuchi;D. Lorenzetti;R. Mawad;G. Stevanin;O. Didierjean;A. Durr;M. Oyake;T. Shimohata;R. Sasaki;R. Koide;S. Igarashi;Shigenobu Hayashi;Y. Takiyama;M. Nishizawa;Hirosato Tanaka;H. Zoghbi;A. Brice;S. Tsuji
为了检验CAG重复数相对较多的正常等位基因（AN）的频率与CAG重复数相对较少的正常等位基因（AN）的频率之间的关系，（大AN）与显性脊髓小脑共济失调（SCA）-SCA 1、2、3型的患病率有关（Machado-Joseph disease），6，和齿状核红核苍白球路易氏体萎缩（DRPLA）-我们调查了这些疾病在202个日本人和177个高加索人家庭中的相对患病率，以及每个群体中正常个体在这些疾病位点上AN的CAG重复序列的数量分布。SCA 1和SCA 2的相对患病率在高加索人家系中（分别为15%和14%）显著高于日本人家系（分别为3%和5%），这与观察到的SCA 1（等位基因>30个重复）和SCA 2（等位基因>22个重复）的大AN频率在高加索人中显著高于日本人相对应。日本家系中MJD/SCA 3、SCA 6和DRPLA的相对患病率显著较高（分别为43%、11%和20%）（分别为30%、5%和0%），这与MJD/SCA 3的大AN频率在日本人中，SCA 6（>27个重复）、SCA 6（>13个重复）和DRPLA（>17个重复）显著高于高加索人。优势SCA的相对患病率与大AN分布的密切相关性强烈支持大AN有助于产生扩展等位基因（AE）和优势SCA的相对患病率的假设。
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.