Takano H, 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
Department of Neurology, Brain Research Institute, Niigata University, Japan.
Am J Hum Genet. 1998 Oct;63(4):1060-6. doi: 10.1086/302067.
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.
为了验证具有相对大量CAG重复序列的正常等位基因（ANs）（大ANs）的频率与显性遗传性脊髓小脑共济失调（SCAs）——1型、2型、3型（马查多-约瑟夫病）、6型以及齿状核红核苍白球路易体萎缩症（DRPLA）的患病率相关这一假设，我们调查了202个日本家庭和177个高加索家庭中这些疾病的相对患病率，以及每个群体中正常个体在这些疾病位点的ANs的CAG重复序列数目的分布情况。SCA1和SCA2在高加索家系中的相对患病率（分别为15%和14%）显著高于日本家系（分别为3%和5%），这与以下观察结果相符：高加索人中SCA1（等位基因>30次重复）和SCA2（等位基因>22次重复）的大ANs频率显著高于日本人。MJD/SCA3、SCA6和DRPLA在日本家系中的相对患病率（分别为43%、11%和20%）显著高于高加索家系（分别为30%、5%和0%），这与以下观察结果相符：日本人中MJD/SCA3（>27次重复）、SCA6（>13次重复）和DRPLA（>17次重复）的大ANs频率显著高于高加索人。显性SCAs的相对患病率与大ANs的分布之间的密切相关性有力地支持了这样一种假设，即大ANs有助于扩展等位基因（AEs）的产生以及显性SCAs的相对患病率。
