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A balanced (1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related psychiatric disorders in a large Scottish family (maximum LOD = 6.0). We hypothesize that the translocation is the causative event and that it directly disrupts gene function. We previously reported a dearth of genes in the breakpoint region of chromosome 11 and it is(More)
The disrupted in schizophrenia 1 (DISC1) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B (PDE4B) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The(More)
To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1. Mice with mutation Q31L showed depressive-like behavior with deficits in the forced swim test and other measures that were reversed by the antidepressant bupropion, but not by rolipram, a(More)
DISC1 is a candidate gene for involvement in the aetiology of major psychiatric illnesses including schizophrenia. We report here the results of DISC1 yeast two-hybrid screens using human foetal and adult brain libraries. Twenty-one proteins from a variety of subcellular locations were identified, consistent with observations that DISC1 occupies multiple(More)
Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate(More)
A systematic survey of 1599 male patients attending a subfertility clinic has shown that 2.2% were chromosomally abnormal. This frequency was approximately five times higher than that found among the normal male population. The majority of chromosome abnormalities (at least in chromatin-negative males) appeared to be exerting their effect on male fertility(More)
Several independent studies have identified Disrupted In Schizophrenia 1 (DISC1) as a potential susceptibility factor in the pathogenesis of schizophrenia and severe recurrent major depression. To identify potential mechanisms by which DISC1 may influence development of psychiatric illness, we investigated the cellular consequences of recombinant DISC1(More)
Disrupted in schizophrenia 1 (DISC1) is one of the most convincing genetic risk factors for major mental illness identified to date. DISC1 interacts directly with phosphodiesterase 4B (PDE4B), an independently identified risk factor for schizophrenia. DISC1-PDE4B complexes are therefore likely to be involved in molecular mechanisms underlying psychiatric(More)
Two candidate genes, DISC1 and DISC2 on chromosome 1, are disrupted by a translocation that segregates with major psychiatric illness. Several DISC1 transcripts contain TRAX (HGMW-approved symbol TSNAX) sequence at the 5' end. These transcripts initiate at the 5' end of TRAX and terminate at the final exon of DISC1. Five species of transcript resulting from(More)