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 24 for “"Germline Mutation"”.
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Germline mutation in rare disease
Germline mutation is the ultimate source of evolutionary change and disease-causing variants. Understanding the rates and patterns of human mutation can help us learn about their molecular origins, uncover our evolutionary history and improve our ability to identify the genetic causes of human …
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Integrated data analytics of germline mutation classes in human cancers. An integrated bioinformatics analysis to investigate associations between germline mutation classes and human cancers.
… project was to investigate the impact of germline gene mutations, as a significant biological factor, on 29 major primary human cancers. For this I obtained data from multiple databases, including the Genetic Association Database (GAD), Sanger database (COSMIC), HGMD database, OMIM data …
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Germline Mutation Detection In Next Generation Sequencing Data and Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome
… transmission information with <em>de novo</em> mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real …
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Second cancers following treatment for retinoblastoma
… a rare childhood tumour of the eye, caused by mutations of the RB1 tumour suppressor gene. However, as survival for retinoblastoma has improved, those with the hereditary form of the disease (RB1 germline mutation) have elevated risks of developing additional cancers, mostly bone and soft …
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Outcomes of Genetic Testing In A Genitourinary Genetics Clinic
… and the probability of having a positive germline mutation if testing is performed. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate whether there is a relationship between the indication for genetic …
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Natural and Exogenous Genome Editing In Wiskott-Aldrich Syndrome Patient Cells
… autoimmunity. This disease is caused by mutations in the WAS gene (<em>WAS</em>) which encodes for the WAS protein (WASp), exclusively expressed in hematopoietic cells and required for proper platelet production and lymphoid cell function. Approximately 11% of patients with WAS exhibit a …
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Attitudes to ward Updated Genetic Testing Among Patients With Unexplained Mismatch Repair Deficiency
… repair (MMR) proteins without a causative germline mutation are said to have unexplained mismatch repair deficiency (UMMRD, also known as mutation-negative Lynch syndrome). Comprehensive genetic testing that could potentially further clarify Lynch syndrome (LS) carrier status is essential …
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Sperm sequencing reveals extensive positive selection in the human germline
… of life, cells of the human body accumulate DNA mutations due to damage from intrinsic causes or exposure to mutagens. Mutations that occur in reproductive cell lineages are known as germline mutations and have the potential to be transmitted to offspring. Germline mutations serve as the origin …
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Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due to Lynch Syndrome?
… </em>promoter hypermethylation and <em>BRAF</em> mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.</p> <p>HYPOTHESIS: …
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Universal Lynch Syndrome Screening in Newly Diagnosed Colorectal Cancer: Impact of an Alberta-wide Screening Program
… in 2-5% of new CRC diagnoses. LS is caused by a germline mutation in one of the DNA Mismatch Repair (MMR) genes and can be diagnosed through germline genetic testing. Universal tumor screening in all new CRCs using Immunohistochemistry (IHC) to assess for loss of MMR-protein expression allows for …
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Integrative Genetic and Epigenetic Studies to Identify Prostate Cancer Genes at Chromosomal 8p
… homozygous deletion region, we did comprehensive germline and somatic analyses, including germline mutation screen in 96 probands of hereditary prostate cancer families, 10 common SNPs association analyses in sporadic PCa cases and controls, somatic copy number change analyses and promoter …
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Mismatch Repair Deficient Cancer Diagnostic Aspects in Colorectal Cancer and the Role of Urological Cancer in Lynch Syndrome
… or hereditary causes (Lynch syndrome due to a germline mutation in one of the MMR genes ¬- MLH1, MSH2, MSH6, PMS2). The identification of MMR defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment-predictive purposes. The aims of this thesis …
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THE NRF-1/GABP/BRCA1 Transcriptional Network in Mammary Epithelial Differentiation
… haploinsufficiency or loss of BRCA1, either by germline mutation or sporadic downregulation, blocks differentiation producing a pool of genetically unstable mammary stem/progenitor cells that are prime targets for transformation. Thus, investigation of BRCA1 regulation and its role in …
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Human Mutation/substitution Rate: Variability, Modeling And Applications
Mutation generates genetic variation, and in turn selection purges deleterious variants from the population. Understanding both is critical for discovering causal genes and variants behind diseases or making inferences about evolutionary processes. Human mutation rate varies significantly across …
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Elucidating the role of BCL6 in helper T cell activation, proliferation, and differentiation
… antibodies specific for an invading pathogen. Germline BCL6-deficient mouse models limit our ability to study BCL6 function in T cells due to the strong inflammatory responses seen in these mice. To overcome this, our lab has developed a new BCL6 conditional knockout (cKO) mouse using the …
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Investigating the clinicopathological spectrum and associated genetics of colorectal carcinoma in young (<60 years of age) patients in the Western Cape Province
… repair deficient (dMMR) cases, without known germline variants, were investigated with amplicon-based panel next generation sequencing (NGS). Pathogenic or likely pathogenic variants were detected in the corresponding MMR gene in 14 of 18 (78%) MLH1/PMS2-deficient tumours, 5 of 8 (63%) …
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The origin and consequences of mutational processes in the human germline
Mutational processes in the germline tissue can generate heritable genetic variation and have the potential to shape disease risk as well as species evolution. In this dissertation, by leveraging data from multiple sources, I explored three mutational processes in the human germline, each having …
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Merlin Regulation of Mouse Spinal Cord Neural Precursor Cell Function
… cancer predisposition syndrome, caused by a germline mutation in the NF2 tumor suppressor gene, in which affected individuals develop spinal cord (SC) ependymomas. In this dissertation, we use NF2 as a tractable genetic model system to define the key intracellular signaling pathways that …
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Malignant melanoma-Risk factors and the CDKN2A mutation in relation to phenotypes and other cancers.
… CMM, high-risk families with the unique Swedish germline mutation in CDKN2A(113insArg), as well as study risk factors for CMM in women. Methods: Tumours associated with CMM, in individuals/probands with four or more primary tumours including at least one CMM were genotyped. The probands were …
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An exploration of mutation effect sizes in the nematode Caenorhabditis elegans
<p>Mutation rates vary within and among species, in part reflecting the variable input of the two main sources of mutation, DNA replication errors and DNA damage. In somatic tissues, oxidative damage resulting from free radical attacks on DNA is an important and well-characterized cause of …
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