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

Y. Ichikawa, J. Goto, Masahira 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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 300kb and includes MJD. We also determined the complete sequence (175,330bp) of B445M7, a human BAC clone that contains MJD. The MJD gene was found to span 48,240bp 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 7.5kb. 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.

Original languageEnglish
Pages (from-to)413-422
Number of pages10
JournalJournal of Human Genetics
Volume46
Issue number7
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Machado-Joseph Disease
Clone Cells
Genes
Bacterial Artificial Chromosomes
Polyadenylation
Human Artificial Chromosomes
Cerebellar Ataxia
Cosmids
Messenger RNA
Alternative Splicing
Gene Library
Neurodegenerative Diseases
Northern Blotting
Retina
Testis
Exons
Complementary DNA
Chromosomes

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Ichikawa, Y., Goto, J., Hattori, M., Toyoda, A., Ishii, K., Jeong, S. Y., ... Kanazawa, I. (2001). The genomic structure and expression of MJD, the Machado-Joseph disease gene. Journal of Human Genetics, 46(7), 413-422. https://doi.org/10.1007/s100380170060

The genomic structure and expression of MJD, the Machado-Joseph disease gene. / Ichikawa, Y.; Goto, J.; Hattori, Masahira; Toyoda, A.; Ishii, K.; Jeong, S. Y.; Hashida, H.; Masuda, N.; Ogata, K.; Kasai, F.; Hirai, M.; Maciel, P.; Rouleau, G. A.; Sakaki, Y.; Kanazawa, I.

In: Journal of Human Genetics, Vol. 46, No. 7, 2001, p. 413-422.

Research output: Contribution to journalArticle

Ichikawa, Y, Goto, J, Hattori, M, Toyoda, A, Ishii, K, Jeong, SY, Hashida, H, Masuda, N, Ogata, K, Kasai, F, Hirai, M, Maciel, P, Rouleau, GA, Sakaki, Y & Kanazawa, I 2001, 'The genomic structure and expression of MJD, the Machado-Joseph disease gene', Journal of Human Genetics, vol. 46, no. 7, pp. 413-422. https://doi.org/10.1007/s100380170060
Ichikawa, Y. ; Goto, J. ; Hattori, Masahira ; Toyoda, A. ; Ishii, K. ; Jeong, S. Y. ; Hashida, H. ; Masuda, N. ; Ogata, K. ; Kasai, F. ; Hirai, M. ; Maciel, P. ; Rouleau, G. A. ; Sakaki, Y. ; Kanazawa, I. / The genomic structure and expression of MJD, the Machado-Joseph disease gene. In: Journal of Human Genetics. 2001 ; Vol. 46, No. 7. pp. 413-422.
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