Abstract
Chromosomal abnormalities can be powerful tools to identify genes that influence disease risk. The study of a chromosome translocation that segregated with severe psychiatric illness in a large family led directly to the discovery of a gene disrupted by a chromosomal breakpoint. Disrupted-in-Schizophrenia-1 (DISC1) is now an important candidate risk gene for schizophrenia and affective disorders. We review the work that led up to this discovery and the evidence that it is important in the wider population with schizophrenia and affective disorders. We also discuss the latest findings on the neuronal functions of the protein DISC1 encoded by the gene.
| Original language | English |
|---|---|
| Pages (from-to) | 140-147 |
| Number of pages | 8 |
| Journal | Current Psychiatry Reports |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 2008 |
Keywords
- chromosomal abnormalities
- genes
- disease risk
- chromosome translocation
- psychiatric illness
- Disrupted-in-Schizophrenia-1
- DISC1
- schizophrenia
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In: Current Psychiatry Reports, Vol. 10, No. 2, 04.2008, p. 140-147.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Disrupted-in-Schizophrenia-1
AU - Muir, W.J.
AU - Pickard, B.S.
AU - Blackwood, D.H.R.
N1 - Bassett AS, McGillivray BC, Jones BD, Pantzar JT: Partial trisomy chromosome 5 cosegregating with schizophrenia. Lancet 1988, 1:799–801. CrossRef Sherrington R, Brynjolfsson J, Petursson H, et al.: Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 1988, 336:164–167. CrossRef St Clair D, Blackwood D, Muir W, et al.: No linkage of chromosome 5q11-q13 markers to schizophrenia in Scottish families. Nature 1989, 339:305–309. CrossRef Blackwood DH, He L, Morris SW, et al.: A locus for bipolar affective disorder on chromosome 4p. Nat Genet 1996, 12:427–430. CrossRef Price WH, Strong JA, Whatmore PB, McClemont WF: Criminal patients with XYY sex-chromosome complement. Lancet 1966, 1:565–566. CrossRef Price WH, Whatmore PB: Criminal behavior and the XYY male. Nature 1967, 213:815. CrossRef Jacobs PA, Brunton M, Frackiewicz A, et al.: Studies on a family with three cytogenetic markers. Ann Hum Genet 1970, 33:325–336. CrossRef St Clair D, Blackwood D, Muir W, et al.: Association within a family of a balanced autosomal translocation with major mental illness. Lancet 1990, 336:13–16. CrossRef Blackwood DH, Fordyce A, Walker MT, et al.: Schizophrenia and affective disorders—cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet 2001, 69:428–433. CrossRef Devon RS, Porteous DJ: Physical mapping of a glutamate receptor gene in relation to a balanced translocation associated with schizophrenia in a large Scottish family. Psychiatr Genet 1997, 7:165–169. Muir WJ, Gosden CM, Brookes AJ, et al.: Direct microdissection and microcloning of a translocation breakpoint region, t(1;11)(q42.2;q21), associated with schizophrenia. Cytogenet Cell Genet 1995, 70:35–40. CrossRef Millar JK, Wilson-Annan JC, Anderson S, et al.: Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 2000, 9:1415–1423. CrossRef Millar JK, Christie S, Anderson S, et al.: Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia. Mol Psychiatry 2001, 6:173–178. CrossRef Austin CP, Ma L, Ky B, et al.: DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain. Neuroreport 2003, 14:951–954. CrossRef Kirkpatrick B, Xu L, Cascella N, et al.: DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex. J Comp Neurol 2006, 497:436–450. CrossRef Camargo LM, Collura V, Rain JC, et al.: Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol Psychiatry 2007, 12:74–86. CrossRef Millar JK, Christie S, Porteous DJ: Yeast two-hybrid screens implicate DISC1 in brain development and function. Biochem Biophys Res Commun 2003, 311:1019–1025. CrossRef Morris JA, Kandpal G, Ma L, Austin CP: 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. Hum Mol Genet 2003, 12:1591–1608. CrossRef Miyoshi K, Honda A, Baba K, et al.: Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Mol Psychiatry 2003, 8:685–694. CrossRef Brandon NJ, Handford EJ, Schurov I, et al.: Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol Cell Neurosci 2004, 25:42–55. CrossRef Ozeki Y, Tomoda T, Kleiderlein J, et al.: Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proc Natl Acad Sci U S A 2003, 100:289–294. CrossRef Kamiya A, Kubo K, Tomoda T, et al.: A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nat Cell Biol 2005, 7:1067–1078. CrossRef Taya S, Shinoda T, Tsuboi D, et al.: DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. J Neurosci 2007, 27:15–26. CrossRef Duan X, Chang JH, Ge S, et al.: Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 2007, 130:1146–1158. CrossRef Kanes SJ, Tokarczyk J, Siegel SJ, et al.: Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity. Neuroscience 2007, 144:239–246. CrossRef Bourtchouladze R, Lidge R, Catapano R, et al.: A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4. Proc Natl Acad Sci U S A 2003, 100:10518–10522. CrossRef Millar JK, Pickard BS, Mackie S, et al.: DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 2005, 310:1187–1191. CrossRef Ekelund J, Lichtermann D, Hovatta I, et al.: Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22. Hum Mol Genet 2000, 9:1049–1057. CrossRef Hennah W, Varilo T, Kestila M, et al.: Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hum Mol Genet 2003, 12:3151–3159. CrossRef Ekelund J, Hennah W, Hiekkalinna T, et al.: Replication of 1q42 linkage in Finnish schizophrenia pedigrees. Mol Psychiatry 2004, 9:1037–1041. CrossRef Kockelkorn TT, Arai M, Matsumoto H, et al.: Association study of polymorphisms in the 5′ upstream region of human DISC1 gene with schizophrenia. Neurosci Lett 2004, 368:41–45. CrossRef Kilpinen H, Ylisaukko-Oja T, Hennah W, et al.: Association of DISC1 with autism and Asperger syndrome. Mol Psychiatry 2008, 13:187–196. CrossRef Thomson PA, Harris SE, Starr JM, et al.: Association between genotype at an exonic SNP in DISC1 and normal cognitive aging. Neurosci Lett 2005, 389:41–45. CrossRef Burdick KE, Hodgkinson CA, Szeszko PR, et al.: DISC1 and neurocognitive function in schizophrenia. Neuroreport 2005, 16:1399–1402. CrossRef Liu YL, Fann CS, Liu CM, et al.: A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1: association with impairment of sustained attention. Biol Psychiatry 2006, 60:554–562. CrossRef Callicott JH, Straub RE, Pezawas L, et al.: Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci U S A 2005, 102:8627–8632. CrossRef Low NC, Hardy J: What is a schizophrenic mouse? Neuron 2007, 54:348–349. CrossRef Clapcote SJ, Lipina TV, Millar JK, et al.: Behavioral phenotypes of Disc1 missense mutations in mice. Neuron 2007, 54:387–402. CrossRef Pletnikov MV, Ayhan Y, Nikolskaia O, et al.: Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia. Mol Psychiatry 2008, 13:173–186. CrossRef Macgregor S, Visscher PM, Knott SA, et al.: A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42. Mol Psychiatry 2004, 9:1083–1090. CrossRef Hamshere ML, Bennett P, Williams N, et al.: Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch Gen Psychiatry 2005, 62:1081–1088. CrossRef Curtis D, Kalsi G, Brynjolfsson J, et al.: Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q. Psychiatr Genet 2003, 13:77–84. CrossRef Hwu HG, Liu CM, Fann CS, et al.: Linkage of schizophrenia with chromosome 1q loci in Taiwanese families. Mol Psychiatry 2003, 8:445–452. CrossRef Ekelund J, Hovatta I, Parker A, et al.: Chromosome 1 loci in Finnish schizophrenia families. Hum Mol Genet 2001, 10:1611–1617. CrossRef Hodgkinson CA, Goldman D, Jaeger J, et al.: Disrupted in Schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet 2004, 75:862–872. CrossRef Cannon TD, Hennah W, van Erp TG, et al.: Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short-and long-term memory. Arch Gen Psychiatry 2005, 62:1205–1213. CrossRef Thomson PA, Wray NR, Millar JK, et al.: Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish population. Mol Psychiatry 2005, 10:657–668; 616. CrossRef Qu M, Tang F, Yue W, et al.: Positive association of the Disrupted-in-Schizophrenia-1 gene (DISC1) with schizophrenia in the Chinese Han population. Am J Med Genet B Neuropsychiatr Genet 2007, 144:266–270. Chen QY, Chen Q, Feng GY, et al.: Case-control association study of Disrupted-in-Schizophrenia-1 (DISC1) gene and schizophrenia in the Chinese population. J Psychiatr Res 2007, 41:428–434. CrossRef Hashimoto R, Numakawa T, Ohnishi T, et al.: Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum Mol Genet 2006, 15:3024–3033.
PY - 2008/4
Y1 - 2008/4
N2 - Chromosomal abnormalities can be powerful tools to identify genes that influence disease risk. The study of a chromosome translocation that segregated with severe psychiatric illness in a large family led directly to the discovery of a gene disrupted by a chromosomal breakpoint. Disrupted-in-Schizophrenia-1 (DISC1) is now an important candidate risk gene for schizophrenia and affective disorders. We review the work that led up to this discovery and the evidence that it is important in the wider population with schizophrenia and affective disorders. We also discuss the latest findings on the neuronal functions of the protein DISC1 encoded by the gene.
AB - Chromosomal abnormalities can be powerful tools to identify genes that influence disease risk. The study of a chromosome translocation that segregated with severe psychiatric illness in a large family led directly to the discovery of a gene disrupted by a chromosomal breakpoint. Disrupted-in-Schizophrenia-1 (DISC1) is now an important candidate risk gene for schizophrenia and affective disorders. We review the work that led up to this discovery and the evidence that it is important in the wider population with schizophrenia and affective disorders. We also discuss the latest findings on the neuronal functions of the protein DISC1 encoded by the gene.
KW - chromosomal abnormalities
KW - genes
KW - disease risk
KW - chromosome translocation
KW - psychiatric illness
KW - Disrupted-in-Schizophrenia-1
KW - DISC1
KW - schizophrenia
U2 - 10.1007/s11920-008-0025-2
DO - 10.1007/s11920-008-0025-2
M3 - Article
C2 - 18474207
SN - 1523-3812
VL - 10
SP - 140
EP - 147
JO - Current Psychiatry Reports
JF - Current Psychiatry Reports
IS - 2
ER -