Abstract
Gene expression is a complex cellular phenotype that reflects the state of a cell. The regulation of gene expression is a multi-level interplay of genetics, epigenetics, proteins and environmental triggers. The major focus of this thesis was to improve understanding of genetic regulatory elements and context specificity of gene expression by utilising RNA-sequencing measurements from three disease related primary tissues (subcutaneous adipose, whole blood, and skin) and one immune cell derived cell line (Lymphoblastoid cell lines, LCL).In this thesis I discuss how UK population representative measurements of three heavy metals (lead, mercury and selenium) in blood of healthy individuals associate with gene expression in human tissue. I reveal strong links between mercury concentrations and oxidative phosphorylation associated genes with nuclear gene expression as well as with mitochondrial gene expression that are specific for skin tissue.
I also use allele specific expression (an imbalance of gene expression of two alleles), to characterize tissue specificity of gene expression and to identify regulatory variants within coding sequences and contribute to the understanding the regulatory complexity of gene expression. I show that ‘Stop gain’ variants and coding sequence variations in the 3’UTR region of genes contribute to allele specific expression.
| Date of Award | 1 May 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Kerrin Small (Supervisor) & Jordana Bell (Supervisor) |