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

• We have used the Fugu homologue of the Huntington's disease (HD) gene to test this possibility [4].

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

• Pufflectin differs from mannose-binding lectins purified from the blood plasma of Fugu [12].
• Nitric oxide synthase in the glossopharyngeal and vagal afferent pathway of a teleost, Takifugu niphobles. The branchial vascular innervation [13].
• Genomic structure and sequence of the leukocyte common antigen (CD45) from the pufferfish Fugu rubripes and comparison with its mammalian homologue [14].
• These results imply that torafugu BCL-6 is involved in regulation of B-cell differentiation in torafugu [15].
• Trout CD4L-2 expression is highest in the thymus, similar to mammalian and chicken CD4, whereas Fugu CD4L-1 expression was highest in the spleen [16].

Associations of Takifugu with chemical compounds

• Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes [17].
• We have demonstrated that three genes (dihydrolipoamide succinyltransferase, S31iii125, and S20i15), which are linked to FOS in the familial Alzheimer disease focus (AD3) on human chromosome 14, have homologues in the Fugu genome adjacent to Fugu cFOS [18].
• Salmonid Hox cluster complements seem to be more similar to those of zebrafish (Danio rerio) than medaka (Oryzias latipes) or pufferfish (Sphoeroides nephelus and Takifugu rubripes), as both Atlantic salmon and rainbow trout have retained HoxCb ortholog, which has been lost in medaka and pufferfish but not in zebrafish [19].
• Recombinant Fugu synucleins exhibited differential liposome binding, which was strongest for alpha-synuclein, followed by beta-, gamma2-, and gamma1-synucleins [20].
• To date, this syntenic association of the Fugu C4 and other MHC class III region genes has not been observed in other teleost fish [21].

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

• We have cloned seven Fugu genes which are closely linked to Surfeit genes in two regions of the Fugu genome and have mapped and ordered their human homologues both by PCR analysis of the Genebridge 4 panel of radiation hybrids and by fluorescence in situ hybridization [27].
• The Fugu HD gene is incorrectly processed in mouse cells both in vitro and in vivo which sheds doubt on the usefulness of Fugu genes for transgenesis [4].
• Overall sequence analysis suggests conservation of intron/exon boundaries between Fugu and human CFTR and revealed extensive homology between functional protein domains [1].
• We assessed the status of this unusual locus in the puffer fish, Fugu rubripes, and identified two INK4 genes using degenerate PCR and hybridization analyses [25].
• We demonstrated expression of the putative Fugu collagen X gene by reverse transcription-polymerase chain reaction (RT-PCR) with primers spanning intron 1 [28].

References