The gene for Machado–Joseph disease maps to the same 3-cM interval as the spinal cerebellar ataxia 3 gene on chromosome 14q
The gene for Machado–Joseph disease maps to the same 3-cM interval as the spinal cerebellar ataxia 3 gene on chromosome 14q
复制标题
马查多-约瑟夫病的基因与 14q 染色体上的脊髓小脑共济失调 3 基因映射到相同的 3-cM 间隔
DOI：
10.1006/nbdi.1994.0010
复制
发表时间：
1994
影响因子：
6.1
通讯作者：
A. Brice
中科院分区：
文献类型：
--
作者：
G. Stevanin;P. S. Sousa;G. Cancel;A. Dürr;O. Dubourg;G. Nicholson;J. Weissenbach;E. Jardim;Y. Agid;E. Cassa;A. Brice
马查多-约瑟夫病(MJD)是一种常染色体显性遗传性神经退行性疾病，见于葡萄牙-阿兹罗里亚血统的家族。导致MJD的基因被分配到14Q染色体上一个29厘米的区间。对一个患有MJD的巴西大家系进行了14Q染色体上跨19 cM的6个新的微卫星标记的基因分型。连锁分析和单倍型重建将MJD候选区域缩小到标记D14S280和D14S81之间3 cM的距离，从而允许位置克隆。这一区间还包含脊髓小脑性共济失调3(SCA3)基因，该基因负责I型常染色体显性遗传性小脑性共济失调的遗传亚型，临床上与MJD有关。这一结果支持了一种假设，即同一基因中的异常可能是这两种疾病的原因。这两种疾病之间的微小临床差异可能是等位基因异质性造成的。
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder in families of Portuguese-Azorean ancestry. The gene responsible for MJD has been assigned to a 29-cM interval on chromosome 14q. A large Brazilian family with MJD was genotyped with six new microsatellite markers spanning 19 cM on chromosome 14q. Linkage analysis and haplotype reconstruction reduced the MJD candidate region to a 3-cM interval between markers D14S280 and D14S81, permitting positional cloning. This interval also contains the spinal cerebellar ataxia 3 (SCA3) gene, responsible for a genetic subtype of the type I autosomal dominant cerebellar ataxias, clinically related to MJD. This result supports the hypothesis that abnormalities in the same gene may be responsible for both disorders. The minor clinical differences between the two diseases may result from allelic heterogeneity.