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 18 of 18 for “"germline variants"”.
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Germline variants associated with alternative splicing in colonic mucosa
… similarity. Certain rare, high penetrance variants are well characterized, though these are estimated to account for only ~5% of all CRC cases. The majority of GWASidentified risk SNPs for CRC fall within non-coding regions, and the mechanisms by which the majority of these variants …
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Identification of germline variants that predispose to familial melanoma
… and linkage analysis was established for the variants in the coding region to identify genes with high burden of mutations where the variants segregated with the disease within the pedigrees. The role of non-coding variants and structural variants in melanoma onset was also investigated …
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COMPREHENSIVE WHOLE GENOME SEQUENCING UNRAVELS THE COMPLEX GENOMIC LANDSCAPE OF NEUROBLASTOMA
… – is still lacking. Moreover, while the role of germline variants in the predisposition of NBL is well established, little is known about their contribution to the onset of specific tumor phenotypes. In this dissertation we used publicly available Whole Genome Sequencing data from two NBL …
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Functional analysis of low grade glioma genetic variants using statistics and physics-inspired deep learning methods
… studies (GWAS) have implicated thousands of germline variants in modulating individual's risk of diseases, including cancer. For low grade gliomas (LGGs), at least 25 risk loci have been identified, whose molecular functions, however, remain largely unknown. Understanding how the risk loci …
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CRISPR/Cas9 screenings and in silico investigations nominate low-frequency alterations in DNA repair genes as biomarkers for castration-resistant prostate cancers.
… the joint allele-specific level analysis of germline variants and somatic alterations of 302 DRGs involved in the principal repair pathways while querying the SU2C-PCF dataset of 429 mCRPC. Association of identified DRG defects with patient outcome and response to androgen receptor-signalling …
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Evaluating Cancer Rates, Cancer Types, and Variant Hotspots Between Different Races and Ethnicities in Individuals with Li-Fraumeni Syndrome
… among races and ethnicities. Although a few germline <em>TP53 </em>pathogenic/likely pathogenic (P/LP) variants in those with LFS have been studied and associated with specific populations, such as the South and Southeast Brazil founder variant, p.Arg337His, there still lacks research on the …
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Molecular diagnosis in inherited polycystic kidney disease
… 100% sensitivity and specificity in identifying germline variants in PKD1 and PKD2, the main genes implicated in ADPKD. Data from the first 85 patients to undergo diagnostic sequencing demonstrated that clinically reportable variants were identified in 91% of patients with a typical ADPKD …
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Analysis of variation in protein domain families and interfaces
… databases and resources. Protein domains and variants were analysed in the context of structural clusters (SCs) and functional families (FunFams), which are derived from structurally and functionally related protein domains in Superfamilies classified in CATH (Class, Architecture, Topology, …
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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
… signalling pathways and spectrum of pathogenic variants, we retrospectively identified 197 CRC cases over a 5 year period. Thirty-two mismatch repair deficient (dMMR) cases, without known germline variants, were investigated with amplicon-based panel next generation sequencing (NGS). Pathogenic …
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Computational analysis of effects and interactions among human variants in complex diseases
… Associations Studies (GWAS) found many variants associated with complex diseases. However, the biological and molecular links between these variants and phenotypes are still mostly unknown. Also, even if sample sizes are constantly increasing, the associated variants do not explain all …
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Germline Genetic Determination of Cancer Outcome
… response to cancer is the genetic makeup of the germline. A thorough assessment of the role of germline genetics in melanoma outcome is lacking, partly because of the difficulty in assessing the vast number of genetic variants present in the human population. In this thesis, I describe the …
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EVALUATION OF THE RISK OF SECONDARY LEUKEMIAS IN CANCER SURVIVORS
… malignancies. Moreover, the presence of germline mutations in cancer predisposing genes can increase the risk of t-MNs. Our hypothesis is that chemotherapy can select clones with somatic mutations, leading to secondary neoplasms. We developed and validated a robust experimental and …
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Haplotype-Informed Allelic Imbalance Detection From Rna In Cancer
… public genetic reference data and array derived germline genotypes, from matched blood samples, to impute millions of germline variants for 4,942 patients across 28 TCGA cancer sites, resulting in improved genotype calling and haplotype inference. This latter approach increased our power for …
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Identification of novel genetic determinants in the high prevalence early-onset inflammatory bowel disease population in Scotland
… were gathered. In this cohort, genotyping of germline variants in putative susceptibility genes (NOD1/CARD4, IL23R, ATG16L1, IRGM, FLG) was performed to enable single variant and haplotype-tagging association studies. Genotypic data of population-matched healthy controls were obtained locally …
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Driver genes, mutational signatures and the timing of mutations in oesophageal adenocarcinoma
… of cancer. By studying single nucleotide variants from 43 tumours I was able to identify the signatures of 7 mutational processes acting on the OAC genome. These include ageing, enzymatic DNA damage (by the APOBEC enzymes) and homologous recombination deficiency. Two novel signatures …
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Butyrophilin family genes as putative coeliac disease risk loci
… in the context of CeD, in order to identify germline variants in butyrophilin genes and the γδ T cell receptor (TCR) that may confer increased CeD risk. This project confirmed that the risk associated HLA loci were not sufficient to explain CeD risk in the UK Biobank, an open-access database …
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Modelling the age-dependent dynamics of clonal haematopoiesis
… estimating expansion rates for common driver variants -- our understanding remains incomplete. This thesis addresses two key unanswered questions: how the selective landscape in blood changes across the human lifespan, and how CH can be distinguished from inherited variation in the context of …
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Genetic and Clinical Determinants of Racial/Ethnic Differences In Multiple Myeloma Susceptibility and Outcomes Focusing On Hispanics
… MM prognosis. Moreover, we identified genetic variants within the Wnt/beta-catenin pathway associated with MM risk that vary by race/ethnicity.</p> <p>Our findings may be clinically applicable to filling the knowledge gap regarding the genetic contributors of MM susceptibility and outcomes in …