2024-03-29T14:35:14Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00016951
2022-12-15T03:48:24Z
453:456
471:537:538:1114
Intergenerational Instability of the CAG Repeat of the Gene for Machado-Joseph Disease (MJD1) is Affected by the Genotype of the Normal Chromosome
MJD1遺伝子内のCAGリピート3'末のCGG/GGG多型に関するCAGリピートの世代間における不安定性の分子遺伝学的検討
MJD1遺伝子内のCAGリピート3'末のCGG/GGG多型に関するCAGリピートの世代間における不安定性の分子遺伝学的検討
五十嵐, 修一
107354
Machado-Joseph disease
MJD1 gene
CAG repeat
inter-allelic interaction
gene conversion
マシャドージョセフ病
MJD1 遺伝子
CAG リピート
アリル間相互作用
遺伝子変換
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects the intergenerational instability of the CAG repeat. The [expanded (CAG) n-CGG]/[normal (CAG) n-GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG) n-CGG]/[nomal (CAG) n-CGG] or [expanded (CAG) n-GGG]/[nomal (CAG) n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (<-2 or >2) is 7.7-fold [95% Cl:2.5-23.9] higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold [95% Cl:2.4-23.3] higher in the case of transmission from a parent with the [expanded (CAG) n-CGG]/[normal (CAG) n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG) n-CGG]/[normal (CAG) n-CGG] or [expanded (CAG) n-GGG]/[normal (CAG) n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG) n-CGG]/[nomal (CAG) n-GGG] haplotypes resulted in a 75.2-fold [95% Cl:9.0-625.0] increase in the relative risk compared with that of maternal transmission and the [expanded (CAG) n-CGG]/[normal (CAG) n-CGG]or[expanded (CAG) n-GGG]/[normal (CAG) n-GGG]haplotypes. The results suggest that an inter-allelic interaction is involved in the intergenarational instability of the expanded CAG repeat.
departmental bulletin paper
新潟医学会
1997-11
application/pdf
新潟医学会雑誌
11
111
691
704
新潟医学会雑誌
AN00182415
00290440
https://niigata-u.repo.nii.ac.jp/record/16951/files/111(11)_691-704.pdf
jpn