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 20 of 60 for “"Rare Variants"”.
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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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Identification and Characterization of Rare Variants in Cholinergic Nicotinic Receptor Genes and their Contribution to Substance Dependence
… to nicotine dependence. However, the role of rare variation in risk for substance dependence in these nicotinic receptor genes has not been studied.</p><p>In order to investigate the role rare variants play in the development of nicotine dependence, we undertook pooled sequencing of the coding …
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Common genetic variants contribute to risk of rare severe neurodevelopmental disorders
… of severe childhood developmental disorders are rare, deleterious, protein-coding changes that cause Mendelian disorders. Children with these disorders typically show early-onset impairment in growth, learning and adaptive behaviours. Linkage and whole exome sequencing studies on these patients …
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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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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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Genetic diversity and population structure within Botswana: association with HIV-1 infection
… there is increasing evidence of the influence of rare variants in the outcome of diseases which may be uncovered by comprehensive complete and deep genome sequencing. This research aimed to characterise human genomic variations of Batswana in order to elucidate mutation burden, assess population …
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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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Genetics of Cerebral Small Vessel Disease
… We next adopt a candidate gene approach to rare variant discovery using high throughput sequencing (HTS) techniques in two forms: 1) a multi-gene sequencing panel to examine the presence of rare variants in a cohort of 993 presumed-sporadic, early-onset SVD stroke patients, and 2) whole …
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Genetic and functional studies in inherited platelet disorders
… loci associated with platelet traits. Common variants, with a minor allele frequency (MAF) ≥1% are associated with mild variation in platelet parameters, whereas rare variants (MAF <1%) are associated with extreme phenotypes and inherited platelet disorders (IPDs). The polygenic score (PGS) …
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Rare Genetic Variants and Cancer Susceptibility
… breast cancer is known to be conferred by common variants, identified through GWAS, together with some rarer variants conferring higher disease risks. The latter, identified through genetic linkage or targeted sequencing studies, includes protein-truncating variants and some rare missense variants …
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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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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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Characterisation of Rare Genetic Variants Conferring Susceptibility to Psoriasis
… unexplained, suggesting the possibility that rare variants may also be pathogenic. The aim of this project was to further investigate this hypothesis and explore different approaches to the identification of rare susceptibility alleles. A candidate gene approach was initially undertaken, …
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Network based analysis of genetic disease associations
… increasingly the prevailing view is that common variants, the target of GWAS, are not solely responsible for susceptibility to common diseases and a substantial portion of human disease risk will be found among rare variants. Relatively new, such variants have not been subject to purifying …
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MOLECULAR PATHWAYS ANALYSIS THROUGH MULTI-OMICS APPROACHES TO STUDY THE BIOLOGICAL BASIS OF ANOREXIA NERVOSA
… patients using a panel of 162 genes to identify rare variants associated with the disorder. The second case study expanded the cohort to 135 AN patients and included the calculation of PRS using a newly designed panel of 163 genes and 730 single nucleotide polymorphisms. The third case study …
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Interactive pedigree plotter for genetic analysis
… in the DNA that may be an attributing factor to rare diseases. One method to analyze these rare variants is to use pedigrees, but because of the low penetrance of these variants, the researcher may have to draw very large pedigrees, hundreds or even thousands of individuals, just to understand …
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Computational methods for the analysis of next generation sequencing data
… are developed and implemented for detecting variants in analysis of individual or pooled DNA sequencing data. SNVer formulates variant calling as a hypothesis testing problem and employs a binomial-binomial model to test the significance of observed allele frequency by taking account of …
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Linear mixed model for multi-level omics data
… demonstrated knowledge (Ashley, 2015). While rare genetic variants, multi-omic information and family structure have provided unprecedented data resources for predictive studies, few related analytical approaches were developed in predicting the risk of complex traits. In the first project, I …
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Sequencing in Isolation: Next-generation sequencing studies in founder populations
Although common variants are routinely assayed in populations, rare mutations and copy-number variants are understudied contributors to the aetiology of complex traits. Isolated populations hold the promise of increased power gains in detecting associations in rare and low-frequency variants that …
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DISSECTING THE POLYGENIC LANDSCAPE OF HUMAN COMPLEX TRAITS AND DISEASES IN A SOUTHERN ITALIAN COHORT
… are shaped by the combined effects of common and rare genetic variants, yet their contribution to risk is still poorly characterised in Southern European populations. This thesis addresses this gap by analysing the genetic architecture of traits and diseases in Italy, leveraging the Moli-sani …
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