EXPANSION OF AN UNSTABLE TRINUCLEOTIDE CAG REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-1
EXPANSION OF AN UNSTABLE TRINUCLEOTIDE CAG REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-1
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DOI：
10.1038/ng0793-221
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发表时间：
1993-07-01
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：
ORR, HT;CHUNG, MY;ZOGHBI, HY
脊髓小脑性共济失调1型(SCA1)是一种常染色体显性遗传性疾病，以小脑、脊髓和脑干的神经变性为特征。在酵母人工染色体重叠群中，从含有SCA1基因的6号染色体短臂中分离出一段1.2兆碱基的DNA片段，并将其亚克隆到粘粒中。在该区域发现了一个高度多态的CAG重复序列，并且在SCA1患者中被发现是不稳定的和扩增的。(CAG)n重复扩增的大小与SCA1的发病年龄直接相关，较大的等位基因出现在青少年病例中。我们还发现该重复序列存在于10千碱基的mRNA转录本中。因此，SCA1是第五种表现出涉及不稳定三核苷酸重复的突变机制的遗传疾病。
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder characterized by neurodegeneration of the cerebellum, spinal cord and brainstem. A 1.2-Megabase stretch of DNA from the short arm of chromosome 6 containing the SCA1 locus was isolated in a yeast artificial chromosome contig and subcloned into cosmids. A highly polymorphic CAG repeat was identified in this region and was found to be unstable and expanded in individuals with SCA1. There is a direct correlation between the size of the (CAG)n repeat expansion and the age-of-onset of SCA1, with larger alleles occurring in juvenile cases. We also show that the repeat is present in a 10 kilobase mRNA transcript. SCA1 is therefore the fifth genetic disorder to display a mutational mechanism involving an unstable trinucleotide repeat.