@article{oai:niigata-u.repo.nii.ac.jp:00016490,
 author = {高野, 弘基},
 issue = {8},
 journal = {新潟医学会雑誌, 新潟医学会雑誌},
 month = {Aug},
 note = {Expansions of CAG repeats have been identified as the causative mutations for 6 dominant spinocerebellar ataxias (SCAs) including spinocerebellar ataxia type 1 (SCA 1), SCA 2, Machado-Joseph disease (MJD)/SCA 3, SCA 6, SCA 7, and dentatorubralpallidoluysian atrophy (DRPLA). The prevalence rate of each of the dominant SCAs considerably differs among the ethnic backgrounds with DRPLA and SCA 6 being more frequent in Japanese than in Caucasian. The basis for the differences in the prevalence rates, however, have not been fully understood. We hypothesized that expanded alleles (AE) arise from the normal alleles (AN) with relatively large size of CAG rapeats, i.e. intermediate alleles (AI), and the prevalence rates are functions of the frequencies of AI in the popualtions. To test this hypothesis, we investigated the relative prevalence rates of the dominant SCAs in population based 202 Japanese and 177 Caucasian familes with dominant SCAs. The distributions of the size of CAG repeats on AN at the 5 loci of unrelated individuals in each population were also determined. The relative prevalence rates of SCA 1 and SCA 2 were significantly higher in Caucasian (15 and 14 %, respectively) than in Japanese (3 and 5 %, respectively) (SCA 1 ; χ^2=13.58, df=1, P=0.0002, SCA 2 ; χ^2=8.41, df=1, P=0.0037). The relative prevalence rates of MJD/SCA 3, SCA 6, and DRPLA were significantly higher in Japanese (42, 11, and 20 %, respectively) than in Caucasian (30, 5, and 0 %, respectively) (MJD/SCA 3 ; χ^2=5.05, df=1, P=0.024, SCA 6 ; χ^2=5.05, df=1, P=0.015, DRPLA ; χ^2=38.21, df=1, P<0.0001). The frequencies of AI of SCA 1 (alleles>30 repeats) and SCA 2 (alleles>22 repeat) were significantly over-represented in Caucasian compared to Japanese (SCAI ; χ^2=22.23, df=1, P<0.0001, SCA 2 ; χ^2=14.84, df=1, P=0.0001), which was in good accordance with the higher ralative prevalence rates of SCA 1 and SCA 2 in Caucasian than in Japanese. The frequencies of AI of MJD/SCA 3 (>27 repeats), SCA 6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasian (MJD/SCA 3 ; χ^2=21.16, df=1, P<0.0001, SCA 6 ; χ^2=38.64, df=1, P<0.0001, DRPLA ; χ^2=11.80, df=1, P=0.0006), which was also in accordance with the higher relative prevalence rates of MJD/SCA 3, SCA 6, and DRPLA in Japanese than in Caucasian. Our analyses demonstrated that the differences in the relative prevalence rates of the dominant SCAs were tightly associated with the differences in the frequencies of the AI between Japanese and Caucasian populations.},
 pages = {452--464},
 title = {本邦における優性遺伝性脊髄小脳変性症の頻度に対する分子遺伝学基盤},
 volume = {112},
 year = {1998}
}