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 19 of 19 for “"heteroplasmy"”.
-
Bioinformatic Approaches to Study Mitochondrial DNA Heteroplasmy
… mtDNA coverage needed to accurately estimate heteroplasmy remains to be defined. I approached this issue through comprehensive computational and statistical analysis, establishing standards that can benefit the entire research community. Finally, I developed a computational pipeline for …
-
Mechanisms Controlling the Segregation of Mitochondrial DNA Heteroplasmy
… alongside healthy ones, in a state termed heteroplasmy. In cases where the proportion of mutant to healthy mtDNA molecules reaches a critical threshold, diverse and multisystem pathological phenotypes begin to appear. While an individual’s mtDNA heteroplasmy level is largely dependent on …
-
Decoding Mitochondrial Heteroplasmy: Illuminating Regulatory Pathways via Rpn11, Mocs3, and Beyond
… a detrimental mtDNA mutation and quantify heteroplasmy levels via qPCR, I found that knockdown of ~1% of them can alter the heteroplasmy level during mitotic divisions. Among these candidates, MOCS3, a ubiquitin-pathway-like E1 activating enzyme, and RPN11, a subunit of the 26S proteasome …
-
Theoretical and Statistical Approaches to Understand Human Mitochondrial DNA Heteroplasmy Inheritance
… by a large intergenerational random shift in heteroplasmy level causing uncertainty for genetic counseling. The aim of this dissertation is to gain insight into how human mtDNA heteroplasmy is inherited. By working closely with our experimental collaborators, the computational simulation of …
-
Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation
… dynamics model include: (1) the decay of mtDNA heteroplasmy in blood is exponential and not linear as reported in literature. (2) Blood heteroplasmy measurements are a good proxy for the blood stem cell heteroplasmy. (3) By analyzing our simulation results in tandem with published longitudinal …
-
Optimisation and validation of tools for in situ visualisation of heteroplasmic mtDNA variants.
… a mixture of mutant and wildtype mtDNA, known as heteroplasmy. Developmental and ageing-related expansion of mutant mtDNA heteroplasmy is the leading cause of adult-onset mitochondrial disease, affecting 1 in 5,000 people in the United Kingdom. It plays a role in neurodegenerative disorders like …
-
Population Variation in the Mitochondrial-DNA of Two Marine Organisms: The Hard Shell Clam <i>Mercenaria spp.</i> and the Killifish, <i>Fundulus Heteroclitus</i>
… polymorphism (16.5-19.0 kb) and restriction site heteroplasmy. Size heteroplasmic individuals occurred at a frequencies of 0-89% in clam populations. Restriction site heteroplasmy occurred in 12% of the 317 individuals assayed. Results of the study indicated that although harbouring a wealth of …
-
Somatic cell interspecies nuclear transfer
… the effect of a mixed mitochondrial population (heteroplasmy) on early embryonic development was investigated. Ooplasmic transfer performed in combination with NT procedure indicated presence of foreign mitochondria clustered in a small portion of the cytoplasm in early stages of embryo …
-
Disease susceptibility and phenotypic adaptations as seen through the lens of comparative functional genomics
… and progression. I devised a novel heteroplasmy detection approach that accounts for the circular nature of the mitochondrial genome and efficiently filters out false-positive heteroplasmies caused by nuclear mitochondrial read misalignment. I performed heteroplasmy detection on 573 …
-
Investigating the Regulation of Mitochondrial DNA Dynamics with a Drosophila Model
… proteins essential for energy production. Heteroplasmy, the state of possessing multiple variants of mtDNA, is very common in humans. The levels of these mtDNA variants are subject to genetic drift and selection during development and ageing. Disease symptoms will manifest when a …
-
EXPLORING THE MUTATIONAL LANDSCAPE OF MITOCHONDRIAL GENOME IN HEMATOLOGIC MALIGNANCIES
… variants and confirmed accurate detection of heteroplasmy levels. Finally, analysis of T lymphocytes isolated from DLBCL patients revealed the presence of disease-specific mtDNA mutations in non-neoplastic immune effector cells, suggesting potential implications for immune surveillance. …
-
Mitochondrial Dna Analysis By Pyrosequencing
… ability of pyrosequencing to detect mixtures and heteroplasmy. Additionally, the ability of pyrosequencing to sequence damaged/degraded DNA was evaluated using blood, semen, and saliva samples that were subjected to three different environmental conditions. A blind study will be conducted to …
-
Mitochondrial genome engineering in the murine germline using designer nuclease technology
… both mtZFN and mitoTALEN, leading to a shift in heteroplasmy towards a greater proportion of wild-type mtDNA. Very recently, both, the Minczuk and Moraes laboratories have independently demonstrated, that AAV-targeted delivery of designer nucleases in the tRNAAla mouse, could selectively …
-
Mitochondrial metabolism in cancer transformation and progression
… with increasing levels of m.8993T>G mutation heteroplasmy. I found that impaired utilisation of reduced nicotinamide adenine dinucleotide (NADH) by the mitochondrial respiratory chain leads to cytosolic reductive carboxylation of glutamine as a new mechanism for cytosol-confined NADH recycling …
-
An Analysis of Mitochondrial DNA in Rett Syndrome and Other Neurodegenerative Disorders
… We then examined the state of mtDNA heteroplasmy in the heteroplasmic disease MELAS (mitochondrial encephalomyopathy, lactic acidosis, strokelike symptoms) in single human lymphoblasts and identified an intercellular distribution of mutant and normal mtDNA. This differs from analyses …
-
Language like behavior in protein secondary structure and analysis of mitochondrial genomes and transposable elements in Antarctic notothenioid fishes
… regions in all icefishes, and I also detected heteroplasmy in C. aceratus and C. esox. Given the role of mitochondrial genomes in energy production and other significant biological processes, these extensive genomic changes may provide an insight into their potential contribution in cold …
-
Novel molecular engineering approaches for genotyping and DNA sequencing
… assay and been able to detect as low as 2.5% heteroplasmy in mitochondrial DNA samples, with interrogation of human mitochondrial genome position 8344 which is associated with an important mitochondrial disease (myoclonic epilepsy with ragged red fibers, MERRF); we have also quantified the …
-
Novel time resolved optical and machine learning methods for label free biomedical imaging
… and algorithms for studying mitochondrial heteroplasmy, one of the markers of mitochondrial disorder where the cells or tissues contain a mixture of healthy and diseased mitochondria. The defects in Electron Transport Chain (ETC) are often the causes behind various mitochondrial disorders. …
-
Characterisation of Mitochondrial Dynamics and Mitochondrial DNA Inheritance in Drosophila melanogaster
Mitochondria are dynamic organelles and there is mounting evidence that mitochondrial dysfunction is linked to a variety of diseases. During spermatogenesis in <i>Drosophila melanogaster</i>, the organisation of mitochondrial networks is altered during each stage of development. This thesis is …