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 15 of 15 for “"incomplete penetrance"”.
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Molecular bases, pathogenic mechanisms and possible therapeutic approach in Leber's Hereditary Optic Neuropathy
… such as the male prevalence, the incomplete penetrance and the tissue selectivity. This maternally inherited disease is caused by mutations in mitochondrial encoded genes of NADH ubiquinone oxidoreductase (complex I) of the respiratory chain. The 90% of LHON cases are caused by one …
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Malignant hyperthermia: allele specific expression and mutation screening of the ryanodine receptor 1 : a dissertation presented to Massey University in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry
… levels might provide insight into the observed incomplete penetrance and variations in MH phenotypes between individuals. Firstly, an H4833Y allele-specific PCR (AS-PCR) assay was designed that allowed for the relative quantification of the two RYR1 mRNA alleles in heterozygous samples. In four …
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Evaluation of Current Clinical Criteria For Li-Fraumeni Syndrome In A Diverse Sample of Tp53 Mutation Carriers
… mutations and inherited mutations exhibiting incomplete penetrance were particularly likely to be missed, indicating a need for additional criteria able to identify <em>TP53</em> mutation carriers in the absence of significant family history. Interestingly, in 22 of the 27 families missed by …
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Study of patients with suspected platelet-based bleeding disorders: a search for patients with a defect in the P2Y12 ADP receptor
… disorders and the fact that both conditions show incomplete penetrance consistent with a multifactorial basis for each disorder. The sequencing was performed by Dr Martina Daly in Sheffield. The work in this thesis has led to the identification / characterisation of a patient who is homozygous for …
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The role of phosphoglycerate dehydrogenase in cell proliferation and tumor progression
… is observed and malignant melanoma arises with incomplete penetrance. These data identify PHGDH as the first metabolic enzyme that can be overexpressed in its wild type form and promote cancer initiation and/or progression to a malignant state. We conclude that PHGDH metabolic activity is …
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Omics Approaches to Uncover Germline and Somatic Variation Underlying Inherited Sarcomagenesis
… (p53)</em><em>, </em>but has variable and incomplete penetrance, suggesting additional acquired somatic mutations are necessary for tumorigenesis. In contrast, LFSL has no known cause, although a 10-Mb region in 1q23 has been mapped by linkage analysis as a putative LFSL locus. Therefore, …
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Identification of Mitochondrial Defects and Metabolic Consequences in Lynch Syndrome-Related Endometrial Cancer
… driver of LS-related EC development. However, incomplete penetrance of EC development in women with LS suggests that other modulators are at play. <strong>The broad hypothesis of this dissertation is that MMRd causes consequences beyond hypermutability to impact LS-related EC …
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Genetic Variants and Risk in Sudden Cardiac Death Syndromes
… the patients at highest risk of SCD events. Incomplete penetrance and variable expressivity even amongst individuals with the same diseasecausing mutation indicates the presence of genetic modifiers, including single nucleotide polymorphisms (SNPs). The majority of SCDs occur in patients with …
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Identification of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing
… in an autosomal dominant manner and demonstrates incomplete penetrance, estimated to be 30%.</p> <p>Whole genome sequencing of eleven individuals in three Wilms tumor families was performed to identify the gene(s) responsible for genetic predisposition to Wilms tumor in these families, and to …
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The molecular genetics of bipolar affective disorder : South African populations, endophenotypes, and environmental influence
… epistasis, gene-environment interactions, incomplete penetrance and variable expressivity. In this thesis three strategies were employed to ameliorate these confounding factors. The first strategy was to focus on a theoretically genetically-homogeneous population with BPD. A unique South …
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Investigation of the GATOR1 complex genes in focal cortical dysplasia and focal epilepsy
… with variable severity, variable foci and incomplete penetrance. The function of these genes and the mechanisms of how their mutation cause the disease are not well understood. In vitro studies have recently found that GATOR1 functions to downregulate the mTORC1 signalling pathway in …
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Pathogenicity assessment of genetic variants in von Willebrand disease using quantitative, qualitative, and functional approaches
… phenotype is complicated by factors including incomplete penetrance and the trans-acting effect of the ABO histo-group. High throughput sequencing (HTS) is becoming the standard of care for the diagnosis of inherited bleeding disorders, including VWD. This raises several challenges. First, how …
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Identification of genetic markers associated with growth and morphology quality in senegalese sole (solea senegalensis) to boost aquaculture production
… a hot recombination region although with an incomplete penetrance. In addition to SNP markers, genome information was used for searching and identifying SSR markers. Hence, 108 new SSR markers distributed throughout the genome were identified. They were structured in 13 PCR Multiplex assays …
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Genetic and functional studies in inherited platelet disorders
… causal of IPDs. The contribution of PGS to incomplete penetrance of a subset of rare variants was estimated and this illustrated that potentially causal rare variants need to be considered in the context of an individual’s genetic architecture. The clinical sequelae of carrying a single …
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Common genetic variation and spliceosome variants in rare developmental disorders
… disorders (NDDs). These are likely affecting the penetrance of protein-coding variants as well as expressivity, posing a major challenge in the interpretation of rare variants. An additional challenge is our incomplete understanding of which variants are likely to affect gene function. Due to the …