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Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish.

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.[1]

References

  1. Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish. Maheshwar, M.M., Sandford, R., Nellist, M., Cheadle, J.P., Sgotto, B., Vaudin, M., Sampson, J.R. Hum. Mol. Genet. (1996) [Pubmed]
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