Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652935
Title: Characterisation of DISC1 : a novel gene identified at a chromosomal translocation associated with psychiatric illness
Author: James, R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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Abstract:
DISC1 (Disrupted in Schizophrenia) was identified at the breakpoint of a chromosomal translocation associated with schizophrenia and other psychiatric illnesses in a large Scottish family. Recent linkage studies have also identified the DISC1 locus as a susceptibility factor for schizophrenia in Finnish families and DISC1 is emerging as a candidate gene for psychiatric illness. At the time of identification DISC1 was novel and the function of the DISC1 protein was completely unknown. To characterise the function of DISC1, antibodies were raised against the DISC1 protein using both a peptide and bacterially expressed recombinant protein as the antigen. The resulting antibodies were characterised thoroughly to ensure their specificity for DISC1. Multiple transcripts of DISC1 had been identified and the initial aim was to determine which of the transcripts were translated into functional proteins. Multiple DISC1-related proteins were found to exist in human but only a single isoform was identified in mouse and rat. In addition the protein expression levels of DISC1 were examined in lymphoblastoid cell lines derived from members of the original translocation family. No evidence for a truncated protein resulting from the translocated chromosome was found but preliminary results suggest that levels of DISC1 are significantly reduced in translocation carriers. The subcellular localisation of DISC1 was studied in human neuroblastoma and glioblastoma cell lines. DISC1 was found to colocalise with mitochondria in a cytoskeletal associated with pattern, and in differentiated neuroblastoma cells DISC1 localised to the tips of developing neurites suggesting a possible role in neurite outgrowth. Further characterisation of the function of DISC1 should now focus on its relationship with the mitochondria to ascertain the significance of this association to both the function and subsequent dysfunction of the nervous system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.652935  DOI: Not available
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