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

Y Ichikawa1, J Goto, M Hattori

  • 1Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.

Journal of Human Genetics
|July 14, 2001
PubMed

Insights

Machado-Joseph disease (MJD) is a neurodegenerative disorder caused by CAG repeat expansion in the MJD gene. Researchers elucidated the gene's genomic structure and identified alternative splicing and polyadenylation sites generating diverse MJD transcripts.

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder.
  • Characterized by cerebellar ataxia and associated symptoms.
  • Caused by unstable CAG repeat expansion in the MJD gene on chromosome 14q32.1.

Purpose of the Study:

  • To determine the genomic structure of the MJD gene.
  • To analyze the MJD gene sequence and identify factors contributing to transcript diversity.

Main Methods:

  • Construction of a 300kb contig using cosmid and bacterial artificial chromosome (BAC) clones.
  • Complete sequencing of the B445M7 human BAC clone containing the MJD gene.
  • Northern blot analysis and cDNA library screening to analyze MJD mRNA expression and splicing.

Main Results:

  • The MJD gene spans 48,240bp and contains 11 exons.
  • MJD mRNA is ubiquitously expressed in human tissues, with transcripts of 1.4, 1.8, 4.5, and 7.5kb.
  • Identified three alternative splicing sites and eight polyadenylation signals within the MJD gene.

Conclusions:

  • The genomic structure of the MJD gene has been elucidated.
  • Differential splicing and polyadenylation are responsible for generating diverse MJD mRNA transcripts.
  • Understanding these mechanisms is crucial for Machado-Joseph disease research.

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