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 12 of 12 for “"Variant Interpretation"”.
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User-Centered Design of a Collaborative Genetic Variant Interpretation Tool
Precision genomic medicine relies upon accurate variant knowledge. However, laboratories continue to arrive at discordant interpretations for the same genomic test. Gaps, inconsistencies, and siloing of variant knowledge may contribute to inter-rater discordance in variant interpretation. Our …
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Computational Tools and Analyses for Improved Inference of Variant Effects
… With over 50% of clinically interpreted missense variants classified as “variants of uncertain significance” (VUSes), multiple approaches are needed to improve variant interpretation. Multiplexed assays of variant effect (MAVEs) can experimentally test nearly all possible missense variants in …
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Isoform-Specific Variant and Expression Analysis of Epigenetic Genes in Neurodevelopment and Disease
… the isoform-specific distribution of pathogenic variants and the timing of isoform expression may reveal critical mechanisms underlying these diseases. Aims To assess whether pathogenic missense variants are enriched in regions unique to non-canonical isoforms and whether these isoforms show …
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Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, and Desired Resources
<p>Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the …
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Systematically and proactively testing variant effects for AIRE and SOD1
… 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 current …
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A study of succinate dehydrogenase deficient tumourigenesis: From functional assessment of variant pathogenicity to the discovery of new disease biomarkers
… (RCC) (3) and pituitary adenomas (4). Pathogenic variants in each of the four genes (SDHx) encoding the four sub-components of this complex (SDHA/B/C/D) have been associated with tumourigenesis. Germline pathogenic variants in SDHB account for up to 50% of patients with malignant PPGL and a 5 year …
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Clinical Utility and Impact of Targeted Nucleic Acid Sequencing in Myeloid Malignancies and Precursor Lesions
… (Thermo Fisher). We further compare commercial variant analysis workflows accompanying the panel with a custom analysis pipeline, demonstrating that supplementing commercial filters with manual variant interpretation improves variant detection. We also performed prospective sequencing in …
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Molecular diagnosis in inherited polycystic kidney disease
… (PKD1). This thesis addresses the sequencing and variant interpretation challenges encountered in the molecular diagnosis of PKD. In addition, mechanisms of cyst formation are explored. These studies demonstrate that Whole Genome Sequencing (WGS) is able to overcome pseudogene homology without the …
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NOVEL APPROACHES IN GENETIC VARIANT DISCOVERY AND CLASSIFICATION TACKLING UNSOLVED PROBLEMS IN CANCER CLINICAL GENOMICS
Accurate interpretation of germline and somatic variants plays a pivotal role in clinical practice, providing the foundation for the correct diagnosis and targeted therapy in personalized medicine. However, variant classification is a complex process that requires the integration of multiple, often …
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Development of a framework for multiomic analysis in disease research
… the return of results from the 100KGP, the NIGMC variant interpretation process was evaluated and genetic analysis was conducted of tier 3 variants, in this instance focusing on renal phenotypes. Several tier 3 variants of interest were identified for further follow up in a postdoctoral research …
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Computational methods for inferring regulatory mechanisms from sequence and expression variation
… technologies, more and more novel genetic variants are being detected. Numerous human genetic and bioinformatic studies associate genotype data to phenotype information and provide increasing number of phenotype-related variants. Despite the large number of associations been detected, we …
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Genetic basis of inherited kidney and related tumours
… for the molecular investigation, germline variant interpretation and clinical management of patients with syndromic and non-syndromic inherited RCC are suggested. A variety of investigative approaches were utilised for this thesis. Firstly, a service evaluation was undertaken which showed a …