Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia (original) (raw)
- Original Research Article
- Published: 17 April 2001
- S Christie1,
- S Anderson1,
- D Lawson1,
- D Hsiao-Wei Loh1,
- R S Devon1,
- B Arveiler2,
- W J Muir1,3,
- D H R Blackwood1,3 &
- …
- D J Porteous1
Molecular Psychiatry volume 6, pages 173–178 (2001)Cite this article
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Abstract
Two overlapping and antiparallel genes on chromosome 1, Disrupted In Schizophrenia 1 and 2 (DISC1 and DISC2), are disrupted by a (1;11)(q42.1;q14.3) translocation which segregates with schizophrenia through at least four generations of a large Scottish family. Consequently, these genes are worthy of further investigation as candidate genes potentially involved in the aetiology of major psychiatric illness. We have constructed a contiguous clone map of PACs and cosmids extending across at least 400 kb of the chromosome 1 translocation breakpoint region and this has provided the basis for examination of the genomic structure of DISC1. The gene consists of thirteen exons, estimated to extend across at least 300 kb of DNA. The antisense gene DISC2 overlaps with exon 9. Exon 11 contains an alternative splice site that removes 66 nucleotides from the open reading frame. The final intron of DISC1 belongs to the rare AT-AC class of introns. We have also mapped marker DIS251 in close proximity to DISC1, localising the gene within a critical region identified by several independent studies. Information regarding the structure of the DISC1 gene will facilitate assessment of its involvement in the aetiology of major mental illness in psychotic individuals unrelated to carriers of the translocation.
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Acknowledgements
We thank Kathy Evans for many useful discussions and Caroline Lamb for her contribution to determining the splice site sequences of DISC1. This work was supported by the United Kingdom Medical Research Council and NV Organon.
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Authors and Affiliations
- Medical Genetics Section. The University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland and MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland
J K Millar, S Christie, S Anderson, D Lawson, D Hsiao-Wei Loh, R S Devon, W J Muir, D H R Blackwood & D J Porteous - Laboratoire de Pathologie Moleculaire et Therapie Genique, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, Bordeaux, 33076, Cedex, France
B Arveiler - Department of Psychiatry, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, Scotland
W J Muir & D H R Blackwood
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Millar, J., 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 6, 173–178 (2001). https://doi.org/10.1038/sj.mp.4000784
- Received: 09 May 2000
- Accepted: 28 June 2000
- Published: 17 April 2001
- Issue Date: 01 March 2001
- DOI: https://doi.org/10.1038/sj.mp.4000784