GAMETIC AND SOMATIC TISSUE-SPECIFIC HETEROGENEITY OF THE EXPANDED SCA1 CAG REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-1
GAMETIC AND SOMATIC TISSUE-SPECIFIC HETEROGENEITY OF THE EXPANDED SCA1 CAG REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-1
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DOI：
10.1038/ng0795-344
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发表时间：
1995-07-01
期刊：
影响因子：
30.8
通讯作者：
ZOGHBI, HY
中科院分区：
文献类型：
--
作者：
CHONG, SS;MCCALL, AE;ZOGHBI, HY
脊髓小脑性共济失调1型与SCA1基因内不稳定的CAG重复序列的扩张有关。通过单精子和低拷贝基因组分析，证实了扩增重复序列的雄性配子异质性。外周血的低拷贝基因组分析也揭示了扩展的SCA1等位基因的体细胞异质性，从而建立了该基因座的有丝分裂不稳定性。对一个大的正常等位基因和一个小的受影响的等位基因的比较分析表明，中游猫的散布在稳定长(CAG)(N)伸展中起到了作用。在大脑中，也可以观察到扩展的等位基因的组织特异性嵌合体。精子和血液之间以及大脑内SCA1等位基因异质性的差异与亨廷顿病的发现相似，这表明这两种疾病都有一个共同的组织特异性不稳定机制。
Spinocerebellar ataxia type 1 is associated with expansion of an unstable CAG repeat within the SCA1 gene. Male gametic heterogeneity of the expanded repeat is demonstrated using single sperm and low-copy genome analysis. Low-copy genome analysis of peripheral blood also reveals somatic heterogeneity of the expanded SCA1 allele, thus establishing mitotic instability at this locus. Comparative analysis of a large normal allele and a small affected allele suggests a role of midstream CAT interspersions in stabilizing long (CAG)(n) stretches. Within the brain, tissue-specific mosaicism of the expanded allele is also observed. The differences in SCA1 allele heterogeneity between sperm and blood and within the brain parallels the findings in Huntington disease, suggesting that both disorders share a common mechanism for tissue-specific instability.