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Annotation

Eykelenboom JE, Briggs GJ, Bradshaw NJ, Soares DC, Ogawa F, Christie S, Malavasi EL, Makedonopoulou P, Mackie S, Malloy MP, Wear MA, Blackburn EA, Bramham J, McIntosh AM, Blackwood DH, Muir WJ, Porteous DJ, Millar JK. A t(1;11) translocation linked to schizophrenia and affective disorders gives rise to aberrant chimeric DISC1 transcripts that encode structurally altered, deleterious mitochondrial proteins. Hum Mol Genet . 2012 Aug 1 ; 21(15):3374-86. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Karoly Mirnics, SRF Advisor
Submitted 21 May 2012 Posted 21 May 2012

DISC1 is a well-established gene conferring schizophrenia susceptibility in a subset of patients. This is a multifunctional protein, involved in regulation of neuronal progenitor cell proliferation and migration, and modulation of dendritic spines. This new study highlights a novel role of this gene vis-à-vis pathophysiology of schizophrenia: translocation of the DISC1 gene to a gene on chromosome 11, DISC1 fusion partner 1 (DISC1FP1), results in the production of various aberrant chimeric transcripts with novel protein-coding potential. This results in the formation of abnormally large protein assemblies that exhibit increased thermal stability, and these abnormal chimeric proteins have a potential to induce abnormal mitochondrial morphology and abolish mitochondrial membrane potential.

We have known for more than a decade that mitochondrial dysfunction/energy metabolism in schizophrenia and bipolar disorder appear to be an integral part of the disease process, but to date it remains unclear if these changes are primary and whether they directly contribute to the disease...  Read more


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Primary News: New Details About DISC1’s Role in Cellular Compartments Emerge

Comment by:  Verian Bader
Submitted 1 June 2012 Posted 1 June 2012

A couple of recently published papers have provided insights into the cell physiology of DISC1. Although DISC1 is one of the most extensively studied susceptibility genes for psychiatric illness, the promoter of DISC1 has not been characterized so far. In a systematic approach based on luciferase reporter genes, Walker et al. (Walker et al., 2012) describe a repressive and an enhancing promoter region upstream of the transcription start. The DISC1 promoter is negatively regulated by FOXP2; hence, affected FOXP2 mutation carriers might show a higher DISC1 expression. Therefore, it would be interesting to know if these FOXP2 mutation carriers also display a higher level of insoluble DISC1, since increased expression leads to an increase of insoluble DISC1 (Leliveld et al., 2008). As a result, and possibly through aggregation, DISC1 loses its ability to bind to specific interaction partners, thereby disrupting some cellular pathways (Atkin et...  Read more


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