title: The genomic structure and expression of MJD, the Machado-Joseph disease gene.
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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: J
authors.initials: J
authors.lastname: Goto
authors.forename: M
authors.initials: M
authors.lastname: Hattori
authors.forename: A
authors.initials: A
authors.lastname: Toyoda
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: S Y
authors.initials: SY
authors.lastname: Jeong
authors.forename: H
authors.initials: H
authors.lastname: Hashida
authors.forename: N
authors.initials: N
authors.lastname: Masuda
authors.forename: K
authors.initials: K
authors.lastname: Ogata
authors.forename: F
authors.initials: F
authors.lastname: Kasai
authors.forename: M
authors.initials: M
authors.lastname: Hirai
authors.forename: P
authors.initials: P
authors.lastname: Maciel
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Y
authors.initials: Y
authors.lastname: Sakaki
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000067699:Ataxin-3; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D020451:Contig Mapping; D003360:Cosmids; D005091:Exons / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007438:Introns / Q000235:genetics*; D017827:Machado-Joseph Disease / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3