The genomic structure and expression of MJD, the Machado-Joseph disease gene

被引：0

作者：

Y. Ichikawa

J. Goto

M. Hattori

A. Toyoda

K. Ishii

S.-Y. Jeong

H. Hashida

N. Masuda

K. Ogata

F. Kasai

M. Hirai

P. Maciel

G. A. Rouleau

Y. Sakaki

I. Kanazawa

机构：

[1] Department of Neurology,

[2] Graduate School of Medicine,undefined

[3] The University of Tokyo,undefined

[4] 7-3-3 Hongo,undefined

[5] Bunkyo-ku,undefined

[6] Tokyo 113-8655,undefined

[7] Japan Tel. +81-3-5800-8672; Fax +81-3-5800-6548 e-mail: gotoj-tky@umin.ac.jp,undefined

[8] CREST,undefined

[9] Japan Science and Technology Corporation,undefined

[10] Saitama,undefined

[11] Japan,undefined

[12] RIKEN Genomic Science Center,undefined

[13] Yokohama,undefined

[14] Japan,undefined

[15] Department of Integrated Biosciences,undefined

[16] Graduate School of Frontier Sciences,undefined

[17] The University of Tokyo,undefined

[18] Tokyo,undefined

[19] Japan,undefined

[20] UnIGENe,undefined

[21] IBMC University of Porto,undefined

[22] Porto,undefined

[23] Portugal,undefined

[24] Centre for Research in Neuroscience,undefined

[25] McGill University and the Montreal General Hospital Research Institute,undefined

[26] Montreal,undefined

[27] Québec,undefined

[28] Canada,undefined

来源：

Journal of Human Genetics | 2001年 / 46卷

关键词：

Key words Machado-Joseph disease (MJD); 14q32.1; CAG repeat; Genome structure; Alternative splicing; mRNA expression;

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摘要：

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder that is clinically characterized by cerebellar ataxia and various associated symptoms. The disease is caused by an unstable expansion of the CAG repeat in the MJD gene. This gene is mapped to chromosome 14q32.1. To determine its genomic structure, we constructed a contig composed of six cosmid clones and eight bacterial artificial chromosome (BAC) clones. It spans approximately 300 kb and includes MJD. We also determined the complete sequence (175,330 bp) of B445M7, a human BAC clone that contains MJD. The MJD gene was found to span 48,240 bp and to contain 11 exons. Northern blot analysis showed that MJD mRNA is ubiquitously expressed in human tissues, and in at least four different sizes; namely, 1.4, 1.8, 4.5, and 7.5 kb. These different mRNA species probably result from differential splicing and polyadenylation, as shown by sequences of the 21 independent cDNA clones isolated after the screening of four human cDNA libraries prepared from whole brain, caudate, retina, and testis. The sequences of these latter clones relative to the MJD gene in B445M7 indicate that there are three alternative splicing sites and eight polyadenylation signals in MJD that are used to generate the differently sized transcripts.

引用

页码：413 / 422

页数：9