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.
Results
Showing 1 to 20 of 35 for “"rare variant"”.
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Mechanism of Rare Variant In Acta2, P.Arg149Cys, Driving Diverse Vascular Disease
<p>Heterozygous variants in <em>ACTA2</em> (smooth muscle (SM) α-actin) predispose to thoracic aortic aneurysms and dissections (TAAD) and early-onset coronary artery disease (CAD). The most common <em>ACTA2</em> mutation is a genetic alteration of arginine 149 to a cysteine, <em>ACTA2</em> …
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Principled "convergence" non-coding rare variant association testing in complex disease
… work. We overcome some of the limitations of rare variant studies by conducting weighted aggregate association tests in a framework we call "Convergence". We compare potential cell type specific regulatory loci assigned to genes, which serve as the basis for grouping variants and integrated …
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Rare Variant Association Studies In Crohn’S Disease and Colorectal Cancer: Methods and Applications
… these diseases, but disease susceptibility from rare variants is incompletely understood. This dissertation includes three chapters, two association studies for Crohn’s disease and CRC, and a statistical method to improve the power of statistical tests.</p> <p>For Crohn’s disease, we performed …
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Recessive and rare variant effects on common diseases and the immune cell transcriptome
… better therapeutics. Different types of variant effects contribute to the heritability of a trait, and in this thesis I focused on recessive effects and rare, loss-of-function variant (LoF) effects. Genes & Health (G&H) is a cohort of ~50,000 British South Asians with elevated rates of …
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Investigating the role of demography and selection in genome scale patterns of common and rare variant diversity in humans
… picture of the patterns of functional and rare variants worldwide high coverage WGS data from 483 individuals (including 379 novel genomes) were analysed. Ingenuity Variant Analysis and the Ensembl Variant Effect Predictor were applied to a subset of these genomes (n = 382) to create a …
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Integration of common and rare genetic variation across complex traits and neuropsychiatric disorders
… identified thousands of links between common variants and phenotypic outcomes. More recently, whole exome and genome sequencing has catalogued patterns of ultra-rare variation and associations with complex traits and diseases. However, there has been relatively little progress integrating the …
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Molecular Mechanisms of Vascular Disease In Patients With Rare Variants In Myh11
… smooth muscle specific myosin heavy chain, are a rare cause of inherited TAAD. However, rare but recurrent non-synonymous variants in <em>MYH11</em> are present in the general population but do not cause inherited TAAD. The goal of this study was to assess the potential role of these rare variants …
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Understanding the Aetiology of Metabolic Diseases and Related Phenotypes through Human Genetics
… gene-disease associations by analysing rare variants that can lead to significant changes in protein function, thereby establishing clear links between protein functions and diseases. Another important method, Mendelian randomisation (MR), leverages genetic variants as natural …
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Multiple Testing Embedded in an Aggregation Tree With Applications to Omics Data
… second part of this dissertation is motivated by rare variant association studies, where a key goal is to identify regions of rare variants, which are associated with disease. This problem is addressed via a flexible method called stochastic aggregation tree-embedded testing (SATET). SATET embeds …
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Development of computational approaches for whole-genome sequence variation and deep phenotyping
The rare disease pulmonary arterial hypertension (PAH) results in high blood pressure in the lung caused by narrowing of lung arteries. Genes causative in PAH were discovered through family studies and very often harbour rare variants. However, the genetic cause in heritable (31%) and idiopathic …
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LA VARIANTE ASSOCIATA ALLA LONGEVITA' (LAV) DEL GENE BPIFB4 MODULA eNOS E LA FUNZIONALITA' VASCOLARE
… for a wild type-WT, a Longevity Associated Variant-LAV and a Rare Variant-RV. We have demonstrated the ability of the Longevity Associated Variant of BPIFB4, LAV-BPIFB4, to induce an improvement in vascular reactivity in opposition to changes in age. Thus, LAV-BPIFB4 may provide a potential …
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Genetic and non-genetic determinants of drug response in type 2 diabetes
… by meta-analyses. In addition,downstream rare variant burden test and pathway analyses were performed. </p><p class="MsoNormal" style="text-align:justify;line-height:150%"><b>Results</b>: We showed robust association of metformin use with fasting glucagon likepeptide-1 (GLP-1) levels in …
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Methods for Determining the Genetic Causes of Rare Diseases
… hundreds of thousands of individuals with rare disorders are undergoing whole-genome sequencing in an effort to reveal novel disease aetiologies, increase our understanding of biological processes and improve patient care. However, the power to discover the genetic causes of many …
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Systematically and proactively testing variant effects for AIRE and SOD1
… often unable to determine the pathogenicity of rare variants in disease-associated genes. Under current guidelines, one of the strongest forms of evidence for variant annotation comes from (often cell-based) functional assays of variant impacts. One-at-a-time variant functional assays are the …
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A Novel Role for HAPLN1 in Skeletal Development
… inherited AIS and identified a co-segregating rare variant in the HAPLN1 gene. HAPLN1 encodes Hyaluronan and Proteoglycan Link Protein 1, also known as Cartilage Link Protein, that is reported to stabilize the extracellular matrix (ECM) by binding hyaluronic acid (HA) and proteoglycans in …
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Introducing A Novel Method For Genetic Analysis of Autism Spectrum Disorder
… GWAS are able to identify multiple common risk variants associated with different diseases, these common variants explain only a small portion of disease occurrence. In the case of autism, GWAS has had only limited success in identification of common risk variants. Recent studies suggest that …
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Genomic and metabolomic interrogation of body composition and insulin resistance endotypes
… into underpinning mechanisms is to anchor it on rare and severe disorders of known cause. In the case of this study this means disorders featuring both severe metabolic derangement and perturbation of body composition. Such rare monogenic disorders reveal causal pathways at the extremes, while …
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Assessing Genetic Counselors' Clinical Approach and Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades
<p>Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially …
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Unravelling the relationship between cigarette smoking and language development
… memory (WM). Moreover, recent work linked a rare variant in Resistant to inhibitors of cholinesterase 3 (RIC3; NM_024557.4:c.262G>A, NP_078833.3:p.G88R) to a unique ability to speak backwards, a language skill with hypothesised association with exceptional WM capacity. Could RIC3 variants be …
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Unravelling the genetic relationships between auditory processing and speech and language
… are applied (monogenic, common disease-common variant and common disease-rare variant) to assess the effect of candidate genes on neurodevelopmental measures, including hearing and language phenotypes, in a population cohort (ALSPAC) of more than 14,000 children. To complement these analyses, a …
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