The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

DISC1  -  disrupted in schizophrenia 1

Homo sapiens

Synonyms: C1orf136, Disrupted in schizophrenia 1 protein, KIAA0457, SCZD9
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of DISC1

 

Psychiatry related information on DISC1

  • Significant association with bipolar disorder in women P=0.00026 (P=0.0016 in men and women combined) was detected in a region of DISC1 [6].
  • The results of karyotypic, clinical, and ERP investigations of this family suggest that the recently described genes DISC1 and DISC2, which are directly disrupted by the breakpoint on chromosome 1, may have a role in the development of a disease phenotype that includes schizophrenia as well as unipolar and bipolar affective disorders [7].
  • Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13 [8].
  • A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse [9].
  • In autopsied brains from patients with psychosis and substance abuse, change in subcellular distribution of DISC1 is observed [10].
 

High impact information on DISC1

  • Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory [11].
  • CONCLUSIONS: Specific alleles of the DISC1 and TRAX genes on 1q42 appear to contribute to genetic risk for schizophrenia through disruptive effects on the structure and function of the prefrontal cortex, medial temporal lobe, and other brain regions [11].
  • Here we performed a biochemical analysis of DISC1 protein in a well characterized set of autopsied brains, including brains of patients with SZ, bipolar disorder, and major depression (MD), as well as normal control brains [9].
  • Based on primary expression of DISC1 in hippocampus, we hypothesized that allelic variation at Ser704Cys would have a measurable impact on hippocampal structure and function as assayed via specific hippocampus-related intermediate phenotypes [12].
  • We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene [12].
 

Chemical compound and disease context of DISC1

 

Biological context of DISC1

 

Anatomical context of DISC1

  • Based on these data, we propose that DISC1 is a multifunctional protein whose truncation contributes to schizophrenia susceptibility by disrupting intracellular transport, neurite architecture and/or neuronal migration, all of which have been hypothesized to be pathogenic in the schizophrenic brain [19].
  • Although both full-length and mutant DISC1 are found in microtubule fractions, neither form of DISC1 appears to bind directly to microtubules, but rather do so in a MIPT3-dependent fashion that is stabilized by taxol [19].
  • In cultured hippocampal neurons, DISC1 and FEZ1 colocalized in growth cones [1].
  • DISC1 localizes to the centrosome by binding to kendrin [20].
  • Furthermore, we have been able to provide the first direct evidence that DISC1 is localized to mitochondria in cultured cortical neurons that are dependent on an intact cytoskeleton [21].
 

Associations of DISC1 with chemical compounds

  • Disrupted-in-Schizophrenia-1 (DISC1): A Key Susceptibility Factor for Major Mental Illnesses [10].
  • DISC1 interacts with phosphodiesterase (PDE) 4B that degrades cyclic AMP (cAMP), which may be a regulatory molecule for working memory in the prefrontal cortex [10].
  • CONCLUSIONS: Disc susceptibility testing methods are unreliable at detecting colistin resistance [22].
  • At 1 mg disc-1, MG greatly inhibited the growth of Cl. perfringens alone [5].
  • METHODS: Disc shaped zirconia (In-Ceram Zirconia) and high alumina (Procera AllCeram) ceramic specimens (diameter: 15mm and thickness: 1.2mm) were fabricated according to the manufacturers' instructions [23].
 

Physical interactions of DISC1

  • This domain is independent from the C-terminal Nudel binding domain highlighting the multidomain nature/functionality of the DISC1 protein [21].
  • We examined the expression of DISC1 and these selected binding partners as well as reelin, a protein in a related signaling pathway, in the hippocampus and dorsolateral prefrontal cortex of postmortem human brain patients with schizophrenia and controls [24].
  • A DISC1-binding domain of DBZ reduced the neurite length in PC12 cells after PACAP stimulation and in primary cultured hippocampal neurons [25].
 

Regulatory relationships of DISC1

  • Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3epsilon complex into the axons as a cargo receptor for axon elongation [26].
  • Knockdown of DISC1 or kinesin light chains of Kinesin-1 by RNA interference inhibited the accumulation of Grb2 from the distal part of axons [27].
  • PACAP upregulated DISC1 expression and markedly reduced the association between DISC1 and DBZ in PC12 cells [25].
 

Other interactions of DISC1

  • DISC2 apparently specifies a non-coding RNA molecule that is antisense to DISC1, an arrangement that has been observed at other loci where it is thought that the antisense RNA is involved in regulating expression of the sense gene [16].
  • The present study shows that DISC1 participates in neurite outgrowth through its interaction with FEZ1 [1].
  • Demonstration that the various TRAX/DISC1 transcripts are translated awaits further experimentation [18].
  • Residues 446-533 of DISC1 were essential for the interaction with kendrin [20].
  • Surprisingly, Nudel is seen to differentially associate with mitochondrial markers in comparison to DISC1 [21].
  • DISC1 Interactome  
 

LIST of Interactome partners (tbc)

 

 

Analytical, diagnostic and therapeutic context of DISC1

  • The interaction between DISC1 and kendrin in mammalian cells was demonstrated by an immunoprecipitation assay [20].
  • On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP [32].
  • Converging evidence from cell culture, mice mutants, postmortem brain, and genetics implicates mutant DISC1 in the pathophysiology of schizophrenia and other mental illnesses [33].
  • As a step in evaluating the function of DISC1 and its potential role in human schizophrenia, we have determined its regional expression in the primate brain by in situ hybridization [29].
  • Preliminary clinical experience with the Bryan Cervical Disc Prosthesis [34].

References

  1. Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Miyoshi, K., Honda, A., Baba, K., Taniguchi, M., Oono, K., Fujita, T., Kuroda, S., Katayama, T., Tohyama, M. Mol. Psychiatry (2003) [Pubmed]
  2. Localized wedge-shaped defects of retinal nerve fiber layer and disc hemorrhage in glaucoma. Sugiyama, K., Uchida, H., Tomita, G., Sato, Y., Iwase, A., Kitazawa, Y. Ophthalmology (1999) [Pubmed]
  3. Prevalence of Heterotopic Ossification Following Total Disc Replacement. A Prospective, Randomized Study of Two Hundred and Seventy-six Patients. Tortolani, P.J., Cunningham, B.W., Eng, M., McAfee, P.C., Holsapple, G.A., Adams, K.A. The Journal of bone and joint surgery. American volume (2007) [Pubmed]
  4. An AOA critical issue. Disc replacements: this time will we really cure low-back and neck pain? Boden, S.D., Balderston, R.A., Heller, J.G., Hanley, E.N., Zigler, J.E. The Journal of bone and joint surgery. American volume. (2004) [Pubmed]
  5. Growth-inhibitory effects of Galla Rhois-derived tannins on intestinal bacteria. Ahn, Y.J., Lee, C.O., Kweon, J.H., Ahn, J.W., Park, J.H. J. Appl. Microbiol. (1998) [Pubmed]
  6. Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish population. Thomson, P.A., Wray, N.R., Millar, J.K., Evans, K.L., Hellard, S.L., Condie, A., Muir, W.J., Blackwood, D.H., Porteous, D.J. Mol. Psychiatry (2005) [Pubmed]
  7. Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Blackwood, D.H., Fordyce, A., Walker, M.T., St Clair, D.M., Porteous, D.J., Muir, W.J. Am. J. Hum. Genet. (2001) [Pubmed]
  8. Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Hamshere, M.L., Bennett, P., Williams, N., Segurado, R., Cardno, A., Norton, N., Lambert, D., Williams, H., Kirov, G., Corvin, A., Holmans, P., Jones, L., Jones, I., Gill, M., O'Donovan, M.C., Owen, M.J., Craddock, N. Arch. Gen. Psychiatry (2005) [Pubmed]
  9. A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse. Sawamura, N., Sawamura-Yamamoto, T., Ozeki, Y., Ross, C.A., Sawa, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Disrupted-in-Schizophrenia-1 (DISC1): A Key Susceptibility Factor for Major Mental Illnesses. Sawamura, N., Sawa, A. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  11. Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Cannon, T.D., Hennah, W., van Erp, T.G., Thompson, P.M., Lonnqvist, J., Huttunen, M., Gasperoni, T., Tuulio-Henriksson, A., Pirkola, T., Toga, A.W., Kaprio, J., Mazziotta, J., Peltonen, L. Arch. Gen. Psychiatry (2005) [Pubmed]
  12. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Callicott, J.H., Straub, R.E., Pezawas, L., Egan, M.F., Mattay, V.S., Hariri, A.R., Verchinski, B.A., Meyer-Lindenberg, A., Balkissoon, R., Kolachana, B., Goldberg, T.E., Weinberger, D.R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. In-vitro biological evaluation of some ONS and NS donor Schiff's bases and their metal complexes. Panchal, P.K., Pansuriya, P.B., Patel, M.N. Journal of enzyme inhibition and medicinal chemistry. (2006) [Pubmed]
  14. Delivery and activity of antimicrobial drugs released from human fibrin sealant. Boyce, S.T., Holder, I.A., Supp, A.P., Warden, G.D., Greenhalgh, D.G. The Journal of burn care & rehabilitation. (1994) [Pubmed]
  15. Mueller-Hinton agar is superior to PDM blood agar for detection of methicillin-resistant Staphylococcus aureus. Monsen, T., Persson, S., Edebro, H., Granström, S., Wiström, J. Clin. Microbiol. Infect. (2003) [Pubmed]
  16. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Millar, J.K., Wilson-Annan, J.C., Anderson, S., Christie, S., Taylor, M.S., Semple, C.A., Devon, R.S., Clair, D.M., Muir, W.J., Blackwood, D.H., Porteous, D.J. Hum. Mol. Genet. (2000) [Pubmed]
  17. Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hennah, W., Varilo, T., Kestilä, M., Paunio, T., Arajärvi, R., Haukka, J., Parker, A., Martin, R., Levitzky, S., Partonen, T., Meyer, J., Lönnqvist, J., Peltonen, L., Ekelund, J. Hum. Mol. Genet. (2003) [Pubmed]
  18. Chromosomal location and genomic structure of the human translin-associated factor X gene (TRAX; TSNAX) revealed by intergenic splicing to DISC1, a gene disrupted by a translocation segregating with schizophrenia. Millar, J.K., Christie, S., Semple, C.A., Porteous, D.J. Genomics (2000) [Pubmed]
  19. DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Morris, J.A., Kandpal, G., Ma, L., Austin, C.P. Hum. Mol. Genet. (2003) [Pubmed]
  20. DISC1 localizes to the centrosome by binding to kendrin. Miyoshi, K., Asanuma, M., Miyazaki, I., Diaz-Corrales, F.J., Katayama, T., Tohyama, M., Ogawa, N. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  21. Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site. Brandon, N.J., Schurov, I., Camargo, L.M., Handford, E.J., Duran-Jimeniz, B., Hunt, P., Millar, J.K., Porteous, D.J., Shearman, M.S., Whiting, P.J. Mol. Cell. Neurosci. (2005) [Pubmed]
  22. Comparison of three standardized disc susceptibility testing methods for colistin. Tan, T.Y., Ng, L.S. J. Antimicrob. Chemother. (2006) [Pubmed]
  23. Effect of mechanical cycling on the flexural strength of densely sintered ceramics. Itinoche, K.M., Ozcan, M., Bottino, M.A., Oyafuso, D. Dental materials : official publication of the Academy of Dental Materials. (2006) [Pubmed]
  24. Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Lipska, B.K., Peters, T., Hyde, T.M., Halim, N., Horowitz, C., Mitkus, S., Weickert, C.S., Matsumoto, M., Sawa, A., Straub, R.E., Vakkalanka, R., Herman, M.M., Weinberger, D.R., Kleinman, J.E. Hum. Mol. Genet. (2006) [Pubmed]
  25. A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Hattori, T., Baba, K., Matsuzaki, S., Honda, A., Miyoshi, K., Inoue, K., Taniguchi, M., Hashimoto, H., Shintani, N., Baba, A., Shimizu, S., Yukioka, F., Kumamoto, N., Yamaguchi, A., Tohyama, M., Katayama, T. Mol. Psychiatry (2007) [Pubmed]
  26. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. Taya, S., Shinoda, T., Tsuboi, D., Asaki, J., Nagai, K., Hikita, T., Kuroda, S., Kuroda, K., Shimizu, M., Hirotsune, S., Iwamatsu, A., Kaibuchi, K. J. Neurosci. (2007) [Pubmed]
  27. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. Shinoda, T., Taya, S., Tsuboi, D., Hikita, T., Matsuzawa, R., Kuroda, S., Iwamatsu, A., Kaibuchi, K. J. Neurosci. (2007) [Pubmed]
  28. DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Morris, J.A., Kandpal, G., Ma, L., Austin, C.P. Hum. Mol. Genet. (2003) [Pubmed]
  29. DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain. Austin, C.P., Ma, L., Ky, B., Morris, J.A., Shughrue, P.J. Neuroreport (2003) [Pubmed]
  30. Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Ozeki, Y., Tomoda, T., Kleiderlein, J., Kamiya, A., Bord, L., Fujii, K., Okawa, M., Yamada, N., Hatten, M.E., Snyder, S.H., Ross, C.A., Sawa, A. Proc. Natl. Acad. Sci. U. S. A. (2003) [Pubmed]
  31. Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Miyoshi, K., Honda, A., Baba, K., Taniguchi, M., Oono, K., Fujita, T., Kuroda, S., Katayama, T., Tohyama, M. Mol. Psychiatry. (2003) [Pubmed]
  32. A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions. Ishizuka, K., Paek, M., Kamiya, A., Sawa, A. Biol. Psychiatry (2006) [Pubmed]
  33. Schizophrenia in Translation: Disrupted in Schizophrenia (DISC1): Integrating Clinical and Basic Findings. Roberts, R.C. Schizophrenia bulletin (2007) [Pubmed]
  34. Preliminary clinical experience with the Bryan Cervical Disc Prosthesis. Goffin, J., Casey, A., Kehr, P., Liebig, K., Lind, B., Logroscino, C., Pointillart, V., Van Calenbergh, F., van Loon, J. Neurosurgery (2002) [Pubmed]
 
WikiGenes - Universities