1型脊髓小脑共济失调中不稳定的三核苷酸CAG重复序列的扩增。

Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.

作者信息

Orr H T, Chung M Y, Banfi S, Kwiatkowski T J, Servadio A, Beaudet A L, McCall A E, Duvick L A, Ranum L P, Zoghbi H Y

机构信息

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.

出版信息

Nat Genet. 1993 Jul;4(3):221-6. doi: 10.1038/ng0793-221.

DOI:10.1038/ng0793-221

PMID:8358429

Abstract

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.

摘要

1型脊髓小脑共济失调（SCA1）是一种常染色体显性疾病，其特征是小脑、脊髓和脑干发生神经退行性变。在酵母人工染色体重叠群中分离出了来自6号染色体短臂的一段1.2兆碱基的包含SCA1基因座的DNA片段，并将其亚克隆到黏粒中。在该区域鉴定出一个高度多态性的CAG重复序列，发现其在SCA1患者中不稳定且发生了扩增。（CAG）n重复序列扩增的大小与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。我们还表明该重复序列存在于一个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突变机制的遗传性疾病。