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Disease relevance of Takifugu

  • To define control elements that regulate tissue-specific expression of the cystic fibrosis transmembrane regulator (CFTR), we have sequenced 60 kb of genomic DNA from the puffer fish Fugu rubripes (Fugu) that includes the CFTR gene [1].
  • To characterize the Nr2e1 locus, which may also contain the mouse kidney disease (kd) allele, we compared sequence from human, mouse, and the puffer fish Fugu rubripes [2].
  • The Fugu Mx promoter was inducible by human IFN-beta in the human hepatoma (Huh7) cells and by polyinosinic: polycytidilic acid in the top minnow hepatoma (PLHC-1) cells [3].

Psychiatry related information on Takifugu


High impact information on Takifugu

  • Scn8a is closely related to other sodium channel alpha subunits, with greatest similarity to a brain transcript from the pufferfish Fugu rubripes [5].
  • In order to identify the functionally important domains of this protein, we have cloned and sequenced the homologue of the HD gene in the pufferfish, Fugu rubripes [6].
  • However, the glutamine repeat in Fugu consists of just four residues [6].
  • Duplication, degeneration and subfunctionalization of the nested synapsin-Timp genes in Fugu [7].
  • Analysis of the human and Fugu genomes show that the evolution of Syn-Timp gene families is characterized by duplications, secondary loss and the partitioning of ancestral functions [7].

Biological context of Takifugu

  • Exploiting differences in intronic sequence composition, a statistical model was developed to predict the splicing phenotype of Fugu introns in mammalian systems and was used to engineer the spliceability of a Fugu intron in human cells by insertion of specific sequences, thereby rescuing splicing in human cells [8].
  • In addition, this region of the Fugu genome shows a much greater overall compaction than usual but with significant noncoding homology observed at the PAX6 locus, implying that comparative genomics has identified regulatory elements associated with this gene [9].
  • This region of the Fugu genome shows conservation of synteny with 800-kb sequence of the human genome encompassing the WNT2, CFTR, Z43555, and CBP90 genes [1].
  • Two other genes (SNAI1 and KRML) mapping to human chromosome 20 are also duplicated in Fugu [10].
  • Our analysis reveals extensive gene duplications in the teleost lineage, leading to 56 claudin genes in Fugu [11].

Anatomical context of Takifugu


Associations of Takifugu with chemical compounds


Gene context of Takifugu

  • To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene [22].
  • Here, Fugu gene homologs of all six Surfeit genes (Surf-1 to Surf-6) have been cloned and sequenced, and their gene structure has been compared with that of their mammalian and avian homologs [23].
  • To determine if the overlaps are a result of the conservation of enhancer sequences between paralogous clusters, we compared the Dlx1/2 and the Dlx5/Dlx6 intergenic regions from human, mouse, zebrafish, and from two pufferfish, Spheroides nephelus and Takifugu rubripes [24].
  • Analysis of the Fugu INK4A/B gene and the surrounding 40-kb of genomic DNA did not reveal the presence of any ARF-encoding potential or another related INK4 gene [25].
  • Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function [26].

Analytical, diagnostic and therapeutic context of Takifugu


  1. Genomic sequence analysis of Fugu rubripes CFTR and flanking genes in a 60 kb region conserving synteny with 800 kb of human chromosome 7. Davidson, H., Taylor, M.S., Doherty, A., Boyd, A.C., Porteous, D.J. Genome Res. (2000) [Pubmed]
  2. Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci. Abrahams, B.S., Mak, G.M., Berry, M.L., Palmquist, D.L., Saionz, J.R., Tay, A., Tan, Y.H., Brenner, S., Simpson, E.M., Venkatesh, B. Genomics (2002) [Pubmed]
  3. Molecular cloning of the pufferfish (Takifugu rubripes) Mx gene and functional characterization of its promoter. Yap, W.H., Tay, A., Brenner, S., Venkatesh, B. Immunogenetics (2003) [Pubmed]
  4. Aberrant processing of the Fugu HD (FrHD) mRNA in mouse cells and in transgenic mice. Sathasivam, K., Baxendale, S., Mangiarini, L., Bertaux, F., Hetherington, C., Kanazawa, I., Lehrach, H., Bates, G.P. Hum. Mol. Genet. (1997) [Pubmed]
  5. Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. Burgess, D.L., Kohrman, D.C., Galt, J., Plummer, N.W., Jones, J.M., Spear, B., Meisler, M.H. Nat. Genet. (1995) [Pubmed]
  6. Comparative sequence analysis of the human and pufferfish Huntington's disease genes. Baxendale, S., Abdulla, S., Elgar, G., Buck, D., Berks, M., Micklem, G., Durbin, R., Bates, G., Brenner, S., Beck, S. Nat. Genet. (1995) [Pubmed]
  7. Duplication, degeneration and subfunctionalization of the nested synapsin-Timp genes in Fugu. Yu, W.P., Brenner, S., Venkatesh, B. Trends Genet. (2003) [Pubmed]
  8. Variation in sequence and organization of splicing regulatory elements in vertebrate genes. Yeo, G., Hoon, S., Venkatesh, B., Burge, C.B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  9. Complete sequencing of the Fugu WAGR region from WT1 to PAX6: dramatic compaction and conservation of synteny with human chromosome 11p13. Miles, C., Elgar, G., Coles, E., Kleinjan, D.J., van Heyningen, V., Hastie, N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. Analyses of the extent of shared synteny and conserved gene orders between the genome of Fugu rubripes and human 20q. Smith, S.F., Snell, P., Gruetzner, F., Bench, A.J., Haaf, T., Metcalfe, J.A., Green, A.R., Elgar, G. Genome Res. (2002) [Pubmed]
  11. Extensive expansion of the claudin gene family in the teleost fish, Fugu rubripes. Loh, Y.H., Christoffels, A., Brenner, S., Hunziker, W., Venkatesh, B. Genome Res. (2004) [Pubmed]
  12. Lectins homologous to those of monocotyledonous plants in the skin mucus and intestine of pufferfish, Fugu rubripes. Tsutsui, S., Tasumi, S., Suetake, H., Suzuki, Y. J. Biol. Chem. (2003) [Pubmed]
  13. Nitric oxide synthase in the glossopharyngeal and vagal afferent pathway of a teleost, Takifugu niphobles. The branchial vascular innervation. Funakoshi, K., Kadota, T., Atobe, Y., Nakano, M., Goris, R.C., Kishida, R. Cell Tissue Res. (1999) [Pubmed]
  14. Genomic structure and sequence of the leukocyte common antigen (CD45) from the pufferfish Fugu rubripes and comparison with its mammalian homologue. Díaz del Pozo, E., Beverley, P.C., Timón, M. Immunogenetics (2000) [Pubmed]
  15. Molecular cloning of the BCL-6 gene, a transcriptional repressor for B-cell differentiation, in torafugu (Takifugu rubripes). Ohtani, M., Miyadai, T., Hiroishi, S. Mol. Immunol. (2006) [Pubmed]
  16. Identification and characterization of a second CD4-like gene in teleost fish. Dijkstra, J.M., Somamoto, T., Moore, L., Hordvik, I., Ototake, M., Fischer, U. Mol. Immunol. (2006) [Pubmed]
  17. Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes. Venkatesh, B., Si-Hoe, S.L., Murphy, D., Brenner, S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus). Trower, M.K., Orton, S.M., Purvis, I.J., Sanseau, P., Riley, J., Christodoulou, C., Burt, D., See, C.G., Elgar, G., Sherrington, R., Rogaev, E.I., St George-Hyslop, P., Brenner, S., Dykes, C.W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  19. Evolution of Hox clusters in Salmonidae: a comparative analysis between Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). Moghadam, H.K., Ferguson, M.M., Danzmann, R.G. J. Mol. Evol. (2005) [Pubmed]
  20. Synuclein proteins of the pufferfish Fugu rubripes: sequences and functional characterization. Yoshida, H., Craxton, M., Jakes, R., Zibaee, S., Tavaré, R., Fraser, G., Serpell, L.C., Davletov, B., Crowther, R.A., Goedert, M. Biochemistry (2006) [Pubmed]
  21. Characterisation of a gene cluster in Fugu rubripes containing the complement component C4 gene. Sambrook, J.G., Campbell, R.D., Elgar, G. Gene (2003) [Pubmed]
  22. Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. Sandford, R., Sgotto, B., Aparicio, S., Brenner, S., Vaudin, M., Wilson, R.K., Chissoe, S., Pepin, K., Bateman, A., Chothia, C., Hughes, J., Harris, P. Hum. Mol. Genet. (1997) [Pubmed]
  23. The comparative genomic structure and sequence of the surfeit gene homologs in the puffer fish Fugu rubripes and their association with CpG-rich islands. Armes, N., Gilley, J., Fried, M. Genome Res. (1997) [Pubmed]
  24. Regulatory roles of conserved intergenic domains in vertebrate Dlx bigene clusters. Ghanem, N., Jarinova, O., Amores, A., Long, Q., Hatch, G., Park, B.K., Rubenstein, J.L., Ekker, M. Genome Res. (2003) [Pubmed]
  25. One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus. Gilley, J., Fried, M. Oncogene (2001) [Pubmed]
  26. Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function. Yu, W.P., Pallen, C.J., Tay, A., Jirik, F.R., Brenner, S., Tan, Y.H., Venkatesh, B. Oncogene (2001) [Pubmed]
  27. Extensive gene order differences within regions of conserved synteny between the Fugu and human genomes: implications for chromosomal evolution and the cloning of disease genes. Gilley, J., Fried, M. Hum. Mol. Genet. (1999) [Pubmed]
  28. Identification of the putative collagen X gene from the pufferfish Fugu rubripes. Woods, A., James, C., Underhill, T.M., Beier, F. Gene (2004) [Pubmed]
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