Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 13 of 13 for “"regulatory variants"”.
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FUNCTIONAL ROLE OF NON-CODING REGULATORY VARIANTS IN NEUROBLASTOMA
… evidence suggests that non-coding somatic variants in cancer can contribute to disease, mainly by residing in functional regulatory regions and ultimately affecting gene expression networks. However, their interpretation is challenging. In our recent work, whole-genome sequencing (WGS) data …
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Dissecting the Functional Impacts of Non-Coding Genetic Variation
… traits has been challenging because most of the variants are located outside of protein-coding regions, and determining the effects of such non-coding variants remains difficult. In this dissertation, I evaluate the hypothesis that such non-coding variants contribute to human traits and diseases …
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Functional interpretation of cancer-associated genetic variants
… have hitherto identified several common genetic variants that may significantly modulate cancer susceptibility. However, the precise molecular mechanisms behind these associations remain largely uncharacterized, creating barriers to understanding the biological processes behind oncogenesis. This …
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Using molecular QTLs to identify cell types and causal variants for complex traits
… and yet for most associated loci the causal variants and molecular mechanisms remain unknown. Studies mapping quantitative trait loci (QTLs) for molecular phenotypes, such as gene expression, RNA splicing, and chromatin accessibility, provide rich data that can link variant effects in …
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Influence of mitochondrial and nuclear genomic dysfunction on lipid homeostasis in lipidemic diseases
… associations between mitochondrial and nuclear variants related to mitochondrial dysfunction and lipid metabolism in NCD progression for a South African cohort. To investigate the functional relevance of mitochondrial variation 59 mitochondrial DNA (mtDNA) variants across 11 oxidative …
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The Molecular Mechanism Of The Gwas Association Of The Slc22a1 Locus With Metabolic Traits
… the molecular mechanism by which SLC22A1 and its variants alter plasma acylcarnitine and LDL cholesterol levels. To study the hepatic function of SLC22A1, we generated liver-specific knockout or overexpression mouse models of SLC22A1 and closely examined their acylcarnitine and lipid profiles. We …
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Integrative statistical methods for the genomic analysis of immune-mediated disease
… associations has proved challenging due to the regulatory nature of the majority of signals. In Chapters 2 and 3, I hypothesised that promoter-capture Hi-C (PCHi-C) data might have utility in physically linking disease-associated regulatory variants to their target genes, in a tissue-specific …
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The Search for Regulatory Mutations in Gitelman Syndrome
… given their scarcity, mutations in functional regulatory regions have yet to be determined. Ideal prototypes to study these variants are recessive Mendelian diseases that are relatively common in the population, caused only by biallelic mutations in one gene, have virtually 100% penetrance with …
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The effect of non-coding variants on gene transcription in human blood cell types
… its regulation. During my PhD I have studied the regulatory effects of human genetic variation. To do so I have processed and analysed datasets measuring effects of genetic variants on transcript levels of genes, identified regulatory variants and put them in bigger biochemical and physiological …
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Human population history and genetic adaptation in the Himalayan region
… Tibetans. However, functional studies of EPAS1 variants have not been systematically carried out and it is still unknown which variant(s) are responsible for high altitude adaptation and their mechanism of action. I used both in silico and in vitro studies to explore these topics and validate …
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Common genetic variation and spliceosome variants in rare developmental disorders
… caused by single, deleterious, protein- coding variants, evidence suggests that common variants also contribute to risk for rare, neurodevelopmental disorders (NDDs). These are likely affecting the penetrance of protein-coding variants as well as expressivity, posing a major challenge in the …
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Genetic analysis of grain protein concentration and related traits in the Illinois protein strain recombinant inbred population of maize
… We find that divergent fixation of expression variants in Asn-cycling genes occurred by cycle 65 of selection, and selection for more strongly-expressed alleles of both Opaque2 and the Prolamin-box factor become important in more recent cycles of the Illinois Protein Strains. Using a GWAS …
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Using single-cell RNA sequencing to elucidate the biological basis of IBD and response to therapy
… the effects of IBD-associated genetic variants in an ex vivo setting, while the second project utilised a co-culture model to understand the immune-cell response to anti-TNF therapy. In the first research chapter of this thesis, scRNA-seq was performed on resting PBMCs from healthy …