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Title: Investigations into genetic and epigenetic features in chronic kidney disease
Author: Smyth, Laura Jane
ISNI:       0000 0004 6060 0489
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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Chronic kidney disease (CKD) is defined as a progressive loss of renal function measured through a decline in the estimated glomerular filtration rate. This occurs over months to years and is a significant public health concern with both the incidence and prevalence rates increasing throughout the world. Initial data was obtained from an Infinium HumanMethylation 450K Bead Chip array which investigated a total of 485,577 CpG sites in 255 individuals with CKD and 152 controls with no evidence of renal disease. Laboratory techniques including Sanger and next generation sequencing technologies were employed to elucidate further information regarding the top-ranked genes and microRNAs. Investigations were carried out using a range of samples from individuals with different phenotypes. Blood-derived DNA samples from individuals were also compared to their cell-line transformed equivalent DNA samples to determine the level of agreement between the genetic variation identified within both sample groups. Additionally, a meta-analysis of SNPs was completed for one of the top-ranked genes identified from the methylation analysis. Analysis of the data gained from the methylation array identified several genes and microRNAs which were significantly associated with the CKD population investigated. Further examination of these top-ranked results supported the generated methylation data, led to the identification of several SNPs and determined the differences in expression level between cases and controls. One significant association was determined from the meta-analysis which assessed different populations and ethnicities. The approaches undertaken considered tissue type and employed cost-effective analyses for both discovery and validation in order to explore the biological relevance of the top-ranked genes and microRNAs. The novel findings of both genetic and epigenetic modifications which are significantly associated with CKD, help to contribute to our understanding of the biological mechanisms which contribute to this disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available