Despite the recent introduction of a number of new and more potent anti-rejection drugs, the incidence of rejection and long-term graft survival remain unchanged. There remains a significant difference in long-term graft survival depending on the source of the donor. The purpose of this study was to examine gene expression in the transplanted kidney using microarray technology to identify potential biomarkers that could be used to predict and monitor graft function so that appropriate interventions could be made in the event of graft dysfunction. Over a 5 year period RNA was extracted from 144 donor kidneys that were transplanted. The initial attempts at probe preparation and hybridization were unsuccessful. This led to the development of a new strategy which involved the use of state-of-the-art microarray technology which embraced the advances realised with the completion of the human genome project. Microarray data was analysed using J-Express and Pathway studio. Significance analysis of microarray, hierachical clustering, gene ontology mapping and pathway analysis was performed. The identification of potential biomarkers that had previously been described by other authors validated this approach. In addition novel genes were identified that may have a role as biomarkers of graft function. Other potential biomarkers were identified that represented cellular processes that could be modified by therapeutic intervention thus possibly changing the clinical outcome or allowing monitoring of the success of therapy. Confirmation of previously described biomarkers and the identification of novel potential biomarkers has confirmed that gene expression profiling has a valuable role in identifying processes that are indicative of disease processes including those involved in kidney transplantation. Furthermore with the development of minimally invasive tests to measure these biomarkers, we can potentially change the natural history of the disease process, and hence, preserve graft function and possibly prolong life.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:559519 |
| Date | January 2009 |
| Creators | O'Dair, Jonathan David |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/10877/ |
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