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Differential genome-wide DNA methylation in prostate tumours from South African men
Dissertation (MSc (Human Genetics))--University of Pretoria, 2021.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2022
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| _version_ | 1867613639750451200 |
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| access_status_str | Open Access |
| author2 | Hayes, Vanessa M. |
| author_browse | Hayes, Vanessa M. |
| author_facet | Hayes, Vanessa M. |
| collection | Thesis |
| dc_rights_str_mv | © 2022 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc (Human Genetics))--University of Pretoria, 2021. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/83702 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:39:20.633Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/83702 Differential genome-wide DNA methylation in prostate tumours from South African men Hayes, Vanessa M. jenna8craddock@gmail.com Bornman, Maria S. (Riana) Craddock, Jenna Epigenomics Prostate cancer DNA methylation Bioinformatics African ethnic disparity UCTD Dissertation (MSc (Human Genetics))--University of Pretoria, 2021. Background: DNA methylation is an epigenetic mechanism known to aid the progression of cancer, including prostate cancer. It is part of a cluster of molecular processes that initiate tumorigenesis and drive its early evolution by altering other molecular processes. While studies have looked at DNA methylation in prostate cancer, most have been limited by targeted gene analysis, with further bias towards non-African cohorts. Considering the enhanced coverage of more recent genome-wide arrays, such as the Illumina Infinium HumanMethylationEPIC BeadChip, which measures DNA methylation over more than 850,000 CpG sites genome-wide, many studies that have employed a more global approach to DNA methylation analysis are further limited by frequently utilising lower-coverage arrays. Due to the bias against African cohorts, African-relevant bioinformatic tools for the processing of African DNA methylation data, particularly generated by the EPIC array, are scarce. As a result, the genomic mechanisms that underlie African prostate cancer as well as the contribution of DNA methylation alterations to African prostate cancer are poorly understood. Results: Working with EPIC DNA methylation data, I present a novel established African-relevant genome-wide bioinformatic pipeline for the processing and normalisation of African tumour-derived genome-wide DNA methylation data. Pilot application of this pipeline on prostate tissue identified differentially methylated CpG dinucleotides that may contribute to aggressive prostate cancer in a small cohort of men of South African ancestry. Additionally, I identified top genes in South African prostate cancer that are significantly enriched for differentially methylated CpG sites. Finally, patient-matched genomic-epigenomic data integration revealed preliminary evidence for interplay between these two systems in African prostate cancer, although the identification of DNA methylation signatures would prove more insightful. Conclusions: Ultimately, this work highlights the marginalization of Africans in scientific research. As a preliminary solution to this underrepresentation, this dissertation provides a novel toolset to appropriately handle African DNA methylation data with the ultimate goal of generating a deeper understanding of the genomic mechanisms harboured within African prostate cancer, a field with limited knowledge. Potential improvements to this tool, complications encountered when interpreting epigenome-wide results as well as the near future of cancer genomics is discussed. Australian National Health and Medical Research Council Genetics MSc (Human Genetics) Unrestricted 2022-02-09T08:57:30Z 2022-02-09T08:57:30Z 2022-04 2021 Dissertation * http://hdl.handle.net/2263/83702 DOI: 10.25403/UPresearchdata.19137047 en © 2022 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | Epigenomics Prostate cancer DNA methylation Bioinformatics African ethnic disparity UCTD Differential genome-wide DNA methylation in prostate tumours from South African men |
| title | Differential genome-wide DNA methylation in prostate tumours from South African men |
| title_full | Differential genome-wide DNA methylation in prostate tumours from South African men |
| title_fullStr | Differential genome-wide DNA methylation in prostate tumours from South African men |
| title_full_unstemmed | Differential genome-wide DNA methylation in prostate tumours from South African men |
| title_short | Differential genome-wide DNA methylation in prostate tumours from South African men |
| title_sort | differential genome wide dna methylation in prostate tumours from south african men |
| topic | Epigenomics Prostate cancer DNA methylation Bioinformatics African ethnic disparity UCTD |
| url | http://hdl.handle.net/2263/83702 |