Human Molecular Genetics, Vol 5, 131-137, Copyright © 1996 by Oxford University Press
MM Maheshwar, R Sandford, M Nellist, JP Cheadle, B Sgotto, M Vaudin and JR Sampson
Germ-line mutations of the TSC2 tumour suppressor gene have been identified
in humans with tuberous sclerosis and in the Eker rat. Tuberin, the human
TSC2 gene product, has a small region of homology with rap1GAP and
stimulates rap1 GTPase activity in vitro, suggesting that one of its
cellular roles is to function as a GTPase activating protein (GAP). We have
undertaken a comparative analysis of the TSC2 gene in human and the
pufferfish, Fugu rubripes. In addition to the GAP domain, three other
regions of the proteins are highly conserved (peptide sequence similarity
> 80%). These regions are likely to represent further functional
domains. To facilitate analysis of mutations within these domains we have
determined the genomic structure of the human TSC2 gene. It comprises 41
exons, including exon 31 which was absent from the originally described
spliceoform of the human TSC2 transcript and was identified following exon
prediction from Fugu genomic sequence. These findings support the proposal
of the Fugu genome as a tool for human gene analysis.
ARTICLES
Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish [published erratum appears in Hum Mol Genet 1996 Apr;5(4):562]
Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK.
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