Characterization of the gene causing type 1 spinocerebellar ataxia and identification of the murine homolog
- Baylor College of Medicine, Houston, TX (United States); and others
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder characterized by neurodegeneration of the cerebellum and brainstem. The mutation in SCA1 involves the expansion of a highly polymorphic CAG trinucleotide repeat located within the coding region of a novel gene on the short arm of human chromosome 6. The SCA1 transcript is 10,660 bases and has a wide pattern of expression. The gene product, ataxin-1, is predicted to contain 792-825 amino acids (depending on the size of the CAG repeat on normal alleles) and does not share any homology with any known protein. The structure of this gene is unusual in that it contains seven exons in the 5{prime} untranslated region (5{prime} UTR) and two large exons (2080 and 7805 bp respectively) which contain the coding region, and a 7277 bp 3{prime} untranslated region (3{prime} UTR). In order to identify putative functional domains of ataxin-1 and to investigate the significance of the long 5{prime} UTR, we began characterizing the murine homolog of the SCA1 gene (Sca1). Northern analysis revealed that the size of the Sca1 transcript is approximately 10.5 kb. Sequence analysis of more than 3 kb of the murine gene revealed that Sca1 encodes for a predicted protein of 792 amino acids which shows 89% peptide identity with the human protein. The murine Sca1 gene contains only two CAG repeats suggesting that the polyglutamine tract is not essential for the normal function of this protein. Preliminary analysis of the murine locus suggests that it is very similar to the human locus with two large exons containing the coding region and a very long 3{prime} UTR. Sequence homology between the mouse and human homologs extends into the 5{prime} UTR and 3{prime} UTR with 85% and 63% identity respectively. Detailed characterization of the 5{prime} UTR in the mouse is currently in progress to determine its potential role in the regulation of transcription and/or translation of this gene.
- OSTI ID:
- 133330
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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