Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia

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...

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Published inMolecular psychiatry Vol. 6; no. 2; pp. 173 - 178
Main Authors MILLAR, J. K, CHRISTIE, S, ANDERSON, S, LAWSON, D, LOH, D. Hsiao-Wei, DEVON, R. S, ARVEILER, B, MUIR, W. J, BLACKWOOD, D. H. R, PORTEOUS, D. J
Format Journal Article
LanguageEnglish
Published Basingstoke Nature Publishing Group 01.03.2001
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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.
AbstractList 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.
Audience Academic
Author ARVEILER, B
CHRISTIE, S
BLACKWOOD, D. H. R
MUIR, W. J
LOH, D. Hsiao-Wei
MILLAR, J. K
LAWSON, D
PORTEOUS, D. J
ANDERSON, S
DEVON, R. S
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  organization: Laboratoire de Pathologie Moleculaire et Therapie Genique, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux, France
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  organization: Medical Genetics Sectionn The University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, United Kingdom
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Issue 2
Keywords Psychosis
Human
Translocation
Linkage
Pathophysiology
Chromosome A1
Schizophrenia
Genetics
Language English
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Snippet 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)...
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StartPage 173
SubjectTerms Adult and adolescent clinical studies
Alternative splicing
Antisense DNA
Biological and medical sciences
Cell Line
Chromosome 1
Chromosome mapping
Chromosomes
Cloning
Cosmids
Disc1 protein
Exons
Genes
Genetic aspects
Genetic Linkage
Genetic Markers
Genetics
Genome, Human
Genomes
Genomics
Hospitals
Humans
In Situ Hybridization, Fluorescence
Introns
Localization
Medical sciences
Mental disorders
Methods
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Nucleotides
Proteins
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Psychosis
Risk factors
RNA Splice Sites - genetics
Schizophrenia
Schizophrenia - genetics
Translocation (Genetics)
Translocation, Genetic
Title Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia
URI https://www.ncbi.nlm.nih.gov/pubmed/11317219
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https://search.proquest.com/docview/70789421
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