subject:(MtDNA mutations)

Brigham Young University

1. Benavides, Edgar. Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal.

Degree: PhD, 2006, Brigham Young University

URL: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2299&context=etd

► In this collection of papers I have summarized my investigations into the field of evolutionary genetics and more specifically into patterns of biodiversity and… (more)

▼ In this collection of papers I have summarized my investigations into the field of evolutionary genetics and more specifically into patterns of biodiversity and evolutionary processes. The lizards (and frogs) studied here share common features in that they are largely present in unique environments, which are also regions that are biologically understudied. Most of these taxa show high degrees of endemism, interesting natural history characteristics, and each group manifests distinctive adaptations of general evolutionary interest. My work in the genus Telmatobius has been a progressive approach that began in my MS program, and it first focused on alpha taxonomy, morphological variation, and species boundaries. This work led to new studies initiated and completed at BYU involving further taxonomic revision (Formas et al., 2003; Chapter 1), and then revisiting and re-evaluating species boundaries established earlier (with allozyme markers) and this time with population level molecular (mitochondrial DNA) markers (Chapter 2). Our results indicate that the striking differences in size, coloration and general appearance in the various Lake Titicaca morphotypes are not genetically based. Further, there is evidence that these morphotypes have evolved very rapidly after demographic bottlenecks eroded present genetic variability. Telmatobius frogs of Lake Titicaca are listed by the International (IUCN) as critically endangered. We support this classification and further suggest studies to explore open questions like the possibility of adaptation along ecological resource gradients. Lizards of the genus Microlophus are interesting but for different reasons, and studies of this group constitutes the bulk of my dissertation work. The genus includes both Galapagos insular species, and continental taxa distributed in a linear gradient along > 4000 km of the western coast of South America. In studying Microlophus I first tackled the unresolved phylogenetic relationships within the genus (Chapter 3) and then pay attention to phylogeographic aspects of the most speciose lizard radiation in the Galapagos Archipelago (Chapter 4). Chapter 3 is a single manuscript provisionally accepted in the journal Systematic Biology. This paper introduces the lizard genus Microlophus (“lava lizards”) as a study system, and includes a large nuclear data set accompanied by an equally large mitochondrial data set (7877 characters in total). This paper explicitly differentiates among sequence alignments of gene regions that vary in tempo and class of mutational events. We show that this recognition is important and we suggest ways to appropriately deal with the alignment of multi-locus non-coding DNA data sets. A secondary finding in this study is that mtDNA and nDNA topologies are discordant with each other but that both are strongly supported, and that the nuclear topology is concordant with species distribution patterns along coastal South America. We hypothesize that in this particular region of the tree, the nuclear genome recovers a topology…

Subjects/Keywords: nuclear introns; alignment; length mutations; Microlophus; secondary contact; mitochondrial-nuclear conflict; phylogenetics; Galapagos; mtDNA; phylogeography; nested clade analysis; colonization routes; volcanism; lava lizards; Biology

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APA (6^th Edition):

Benavides, E. (2006). Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal. (Doctoral Dissertation). Brigham Young University. Retrieved from https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2299&context=etd

Chicago Manual of Style (16^th Edition):

Benavides, Edgar. “Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal.” 2006. Doctoral Dissertation, Brigham Young University. Accessed January 22, 2021. https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2299&context=etd.

MLA Handbook (7^th Edition):

Benavides, Edgar. “Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal.” 2006. Web. 22 Jan 2021.

Vancouver:

Benavides E. Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal. [Internet] [Doctoral dissertation]. Brigham Young University; 2006. [cited 2021 Jan 22]. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2299&context=etd.

Council of Science Editors:

Benavides E. Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal. [Doctoral Dissertation]. Brigham Young University; 2006. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2299&context=etd

2. Dovydenko, Ilya. Mise au point d'aptamères aux capacités thérapeutiques basés sur les ARN importables dans les mitochondries humaines : Design of therapeutic RNA aptamers imported into mitochodria ot human cells.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2015, Université de Strasbourg

URL: http://www.theses.fr/2015STRAJ046

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Les défauts de génome mitochondrial provoquent des maladies neuromusculaires, pour lequel aucun traitement efficace n'a été mis au point. La plupart des mutations mitochondriales sont… (more)

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Les défauts de génome mitochondrial provoquent des maladies neuromusculaires, pour lequel aucun traitement efficace n'a été mis au point. La plupart des mutations mitochondriales sont hétéroplasmique, ce qui signifie que l'ADN mitochondrial (ADNmt) de type sauvage et muté coexistent dans la même cellule, et le changement de proportion entre deux types d'ADNmt pourrait rétablir les fonctions mitochondriales. Le but du projet était le développement du système pour cibler l'ARN thérapeutique dans les cellules humaines vivantes. Au cours de ma thèse j'ai synthétisé une série de nouveaux ARN anti-réplicatifs contenant modifications chimiques pour augmenter leur stabilité dans la cellule, et mis au point la nouvelle méthode de synthèse chimique des molécules d'ARN contenant cholestérol fixé par l'intermédiaire d'un pont biodégradable. Ces ARN étaient capable de pénétrer dans les cellules humains, d'être adressées dans les mitochondries et de diminuer la proportion d' ADNmt muté.

Defects in mitochondrial genome cause neuromuscular diseases, for which no efficient therapy has been developed. Since most mitochondrial mutations are heteroplasmic, wild type and mutated mitochondrial DNA (mtDNA) coexist in the same cell, and the shift in proportion between two mtDNA types could restore mitochondrial functions. The aim of the project was development of carrier-free system for targeting the therapeutic mitochondrially importable RNA into living human cells. During my PhD study, I have synthesized a set of new anti-replicative RNAs containing various chemical modifications, aiming to increase their stability in the cell, and developed a new method for the chemical synthesis of RNA molecules containing cholesterol attached through a biodegradable bridge. Cholesterol containing antireplicative RNAs were characterised by efficient cellular uptake, partial colocalisation with mitochondria and ability to decrease the proportion of mutant mtDNA.

Advisors/Committee Members: Entelis, Nina (thesis director), Venyaminova, Alia (thesis director).

Subjects/Keywords: ADN mitochondrial; ADNmt; ARN anti-réplicatif; Mutations mitochondriales hétéroplasmiques; Thérapie génique; Cell delivery; Antireplicative RNA; Cholesterol containing RNA conjugates; Mitochondrial drug delivery; Mitochondrial diseases; Modified oligonucleotides; MtDNA Heteroplasmy; RNA import; 571.6; 572.8

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dovydenko, I. (2015). Mise au point d'aptamères aux capacités thérapeutiques basés sur les ARN importables dans les mitochondries humaines : Design of therapeutic RNA aptamers imported into mitochodria ot human cells. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2015STRAJ046

Chicago Manual of Style (16^th Edition):

Dovydenko, Ilya. “Mise au point d'aptamères aux capacités thérapeutiques basés sur les ARN importables dans les mitochondries humaines : Design of therapeutic RNA aptamers imported into mitochodria ot human cells.” 2015. Doctoral Dissertation, Université de Strasbourg. Accessed January 22, 2021. http://www.theses.fr/2015STRAJ046.

MLA Handbook (7^th Edition):

Dovydenko, Ilya. “Mise au point d'aptamères aux capacités thérapeutiques basés sur les ARN importables dans les mitochondries humaines : Design of therapeutic RNA aptamers imported into mitochodria ot human cells.” 2015. Web. 22 Jan 2021.

Vancouver:

Dovydenko I. Mise au point d'aptamères aux capacités thérapeutiques basés sur les ARN importables dans les mitochondries humaines : Design of therapeutic RNA aptamers imported into mitochodria ot human cells. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2015. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2015STRAJ046.

Council of Science Editors:

Dovydenko I. Mise au point d'aptamères aux capacités thérapeutiques basés sur les ARN importables dans les mitochondries humaines : Design of therapeutic RNA aptamers imported into mitochodria ot human cells. [Doctoral Dissertation]. Université de Strasbourg; 2015. Available from: http://www.theses.fr/2015STRAJ046

3. Gutierrez Cortes, Nicolas. Expression métabolique des polymorphismes mitochondriaux : mutations pathogènes et haplogroupes : Metabolic expression of mitochondrial polymorphisms : pathological mutations and haplogroups.

Degree: Docteur es, Sciences, technologie, santé. Biologie cellulaire et physiopathologie, 2011, Université de Bordeaux Segalen

URL: http://www.theses.fr/2011BOR21877

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Les mitochondries, organelles intracellulaires des eucaryotes, fournissent par les oxydations phosphorylantes l'essentiel de l'énergie nécessaire aux différents travaux cellulaires sous la forme d'ATP grâce à… (more)

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Les mitochondries, organelles intracellulaires des eucaryotes, fournissent par les oxydations phosphorylantes l'essentiel de l'énergie nécessaire aux différents travaux cellulaires sous la forme d'ATP grâce à un couplage entre la chaîne respiratoire et l’ATPsynthase. Ces réactions du métabolisme énergétique sont assurées par des complexes enzymatiques constitués de sous-unités codées à la fois par l'ADN nucléaire et par l'ADN mitochondrial. Il a été montré que des défauts dans l'activité de ces complexes pouvaient être responsables de l’apparition de pathologies regroupées sous le nom de cytopathies d’origine mitochondriale. Un des problèmes fondamentaux qui se pose lors de l’étude des mécanismes conduisant aux pathologies mitochondriales est de comprendre l’influence de l’ADN mitochondrial sur le métabolisme de la mitochondrie. En effet, la mitochondrie possède son propre ADN, et les mutations de cet ADN sont classées selon leur impact sur le métabolisme mitochondrial : des mutations pathogènes, qui ont des répercussions négatives sur ce métabolisme, et des polymorphismes, qui sont considérés comme étant neutres.Pour étudier l’influence de l’ADNmt sur le métabolisme énergétique, j’ai utilisé deux modèles d’étude : des cybrids portant des mutations de l’ADNmt retrouvées chez des patients atteints de surdité non-syndromique, et des cybrids portant des polymorphismes caractéristiques de l’haplogroupe J.Les résultats obtenus nous indiquent clairement que la différence entre des mutations pathogènes et des polymorphismes n’est pas aussi importante que ce qui était jusqu’à alors supposé. En effet, elle dépend d’un ensemble de facteurs tels que (i) le fonds génétique nucléaire et mitochondrial, (ii) de facteurs environnementaux. Car sous l’influence de ces différents facteurs une mutation considérée comme pathogène peut devenir neutre, et un polymorphisme considéré comme neutre peut devenir pathogène.

Mitochondria, intracellular organelles of eukaryotic organisms, provide most of the necessary energy for cellular activity through oxidative phosphorylation, synthesizing ATP (energy source for the cell) by a coupling between the respiratory chain and the ATPsynthase. These energy metabolism reactions are carried out by enzymatic complexes constituted by sub-units coded by both nuclear and mitochondrial DNA. It has been shown that activity defects in these complexes could be responsible for a group of pathologies under the name of mitochondrial cytopathies.One of the fundamental issues of the study of the mechanisms that lead to mitochondrial cytopathies is the understanding of the influence that mitochondrial DNA has over mitochondrial metabolism. Indeed, mitochondria have their own DNA, and mutations in this DNA are classified according to their impact on mitochondrial metabolism: pathological mutations, which have negative consequences on mitochondrial metabolism, and polymorphisms, which are considered to be neutral.In order to study the influence of mtDNA on energy metabolism, I used two different models: cybrid cells…

Advisors/Committee Members: Rocher, Christophe (thesis director).

Subjects/Keywords: Mitochondrie; ADNmt; OXPHOS; Cytopathies d’origine mitochondriale; Mutations de l’ADNmt; Polymorphismes; Haplogroupes; Surdité; Mitochondria; MtDNA; OXPHOS; Mitochondrial cytopathies; MtDNA mutations; Polymorphisms; Polymorphisms, haplogroups; Deafness

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gutierrez Cortes, N. (2011). Expression métabolique des polymorphismes mitochondriaux : mutations pathogènes et haplogroupes : Metabolic expression of mitochondrial polymorphisms : pathological mutations and haplogroups. (Doctoral Dissertation). Université de Bordeaux Segalen. Retrieved from http://www.theses.fr/2011BOR21877

Chicago Manual of Style (16^th Edition):

Gutierrez Cortes, Nicolas. “Expression métabolique des polymorphismes mitochondriaux : mutations pathogènes et haplogroupes : Metabolic expression of mitochondrial polymorphisms : pathological mutations and haplogroups.” 2011. Doctoral Dissertation, Université de Bordeaux Segalen. Accessed January 22, 2021. http://www.theses.fr/2011BOR21877.

MLA Handbook (7^th Edition):

Gutierrez Cortes, Nicolas. “Expression métabolique des polymorphismes mitochondriaux : mutations pathogènes et haplogroupes : Metabolic expression of mitochondrial polymorphisms : pathological mutations and haplogroups.” 2011. Web. 22 Jan 2021.

Vancouver:

Gutierrez Cortes N. Expression métabolique des polymorphismes mitochondriaux : mutations pathogènes et haplogroupes : Metabolic expression of mitochondrial polymorphisms : pathological mutations and haplogroups. [Internet] [Doctoral dissertation]. Université de Bordeaux Segalen; 2011. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2011BOR21877.

Council of Science Editors:

Gutierrez Cortes N. Expression métabolique des polymorphismes mitochondriaux : mutations pathogènes et haplogroupes : Metabolic expression of mitochondrial polymorphisms : pathological mutations and haplogroups. [Doctoral Dissertation]. Université de Bordeaux Segalen; 2011. Available from: http://www.theses.fr/2011BOR21877

Freie Universität Berlin

4. Lüth, Maria. Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors.

Degree: 2011, Freie Universität Berlin

URL: https://refubium.fu-berlin.de/handle/fub188/13747

► To detect somatic mitochondrial DNA mutations in neuroectodermal tumors, mutation analysis in patients with medulloblastoma, pilocytic astrocytoma and neurofibromatosis type 1-associated tumors was performed. MtDNA… (more)

▼ To detect somatic mitochondrial DNA mutations in neuroectodermal tumors, mutation analysis in patients with medulloblastoma, pilocytic astrocytoma and neurofibromatosis type 1-associated tumors was performed. MtDNA alterations in the entire mitochondrial genome were analyzed by temporal temperature gradient gelelectrophoresis followed by DNA sequencing. We have analyzed the entire mitochondrial genome in 15 cases of medulloblastoma and the corresponding cerebrospinal fluid (CSF) samples in 10 of the 15 cases. Six of the fifteen cases (40%) showed at least one mtDNA mutation in the tumors. A total of 18 somatic mtDNA mutations were detected with one of the tumors having 11 mutations of which 9 were novel. Three of the six cases with mtDNA mutation also showed mutation in the cell-free CSF collected at various times during therapy. Somatic mtDNA mutations in tumors were found in 7 of 19 individuals with cutaneous neurofibromas and in 9 of 18 patients with plexiform neurofibromas. A total of 34 somatic mtDNA mutations were found. All mutations were located in the displacement loop region of the mitochondrial genome. Several plexiform neurofibromas from individual patients had multiple homoplasmic mtDNA mutations. In cutaneous neurofibromas, the same mtDNA mutations were always present in tumors from different locations of the same individual. An increase in the proportion of the mutant mtDNA was always found in the neurofibromas when compared with nontumor tissues. The somatic mtDNA mutations were present in the Schwann cells of the analyzed multiple cutaneous neurofibromas of the same individual. The observed dominance of a single mtDNA mutation in multiple cutaneous neurofibromas of individual patients indicates a common tumor cell ancestry and suggests a replicative advantage rather than random segregation for cells carrying these mutated mitochondria. Advisors/Committee Members: [email protected] (contact), w (gender), PD Dr. med. P. Hernáiz-Driever (firstReferee), Prof. Dr. med. M. Hasselblatt (furtherReferee), Prof. Dr. med. F. Aksu (furtherReferee).

Subjects/Keywords: mtDNA; somatic mutations; neurofibromatosis type 1-associated tumors; pilocytic astrocytoma; medulloblastoma; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lüth, M. (2011). Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors. (Thesis). Freie Universität Berlin. Retrieved from https://refubium.fu-berlin.de/handle/fub188/13747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lüth, Maria. “Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors.” 2011. Thesis, Freie Universität Berlin. Accessed January 22, 2021. https://refubium.fu-berlin.de/handle/fub188/13747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lüth, Maria. “Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors.” 2011. Web. 22 Jan 2021.

Vancouver:

Lüth M. Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors. [Internet] [Thesis]. Freie Universität Berlin; 2011. [cited 2021 Jan 22]. Available from: https://refubium.fu-berlin.de/handle/fub188/13747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lüth M. Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors. [Thesis]. Freie Universität Berlin; 2011. Available from: https://refubium.fu-berlin.de/handle/fub188/13747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Tech

5. Rajasimha, Harsha Karur. Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation.

Degree: PhD, Genetics, Bioinformatics, and Computational Biology, 2007, Virginia Tech

URL: http://hdl.handle.net/10919/29961

► MtDNA mutations in mammalian cells are implicated in cellular ageing and encephalomyopathies, although mechanisms involved are not completely understood. The mitochondrial genetic bottleneck has puzzled… (more)

▼ MtDNA mutations in mammalian cells are implicated in cellular ageing and encephalomyopathies, although mechanisms involved are not completely understood. The mitochondrial genetic bottleneck has puzzled biologists for a long time. Approximate models of genetic bottleneck proposed in the literature do not accurately model underlying biology. Recent studies indicate mitochondrial morphology changes during cellular aging in culture. In particular, the rates of mitochondrial fission and fusion are shown to be in tight balance, though this rate decreases with age. Some proteins involved in mitochondrial morphology maintenance are implicated in apoptosis. Hence, mitochondrial genetic and morphologic dynamics are critical to the life and death of cells. By working closely with experimental collaborators and by utilizing data derived from literature, we have developed stochastic simulation models of mitochondrial genetic and morphologic dynamics. Hypotheses from the mitochondrial genetic 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 clinical data, we propose for the first time, a way to correct for the patient's age in the analysis of heteroplasmy data. (4) We develop a direct model of the genetic bottleneck process during mouse embryogenesis. (5) Partitioning of mtDNA into daughter cells during blastocyst formation and relaxed replication of mtDNA during the exponential growth phase of primordial germ cells leads to the variation in heteroplasmy inherited by offspring from the same mother. (6) We develop a “simulation control” for experimental studies on mtDNA heteroplasmy variation in cell cultures. Hypothesis from the mitochondrial morphologic dynamics model: (7) A cell adjusts the mitochondrial fusion rate to compensate for the fluctuations in the fission rate, but not vice versa. A deterministic model for this control is proposed. Contributions: extensible simulation models of mitochondrial genetic and morphologic dynamics to aide in the powerful analysis of published and new experimental data. Our results have direct relevance to cell biology and clinical diagnosis. The work also illustrates scientific success by tight integration of theory with practice. Advisors/Committee Members: Samuels, David C. (committeechair), Tyson, John J. (committee member), Vullikanti, Anil Kumar S. (committee member), Onufriev, Alexey V. (committee member), Bevan, David R. (committee member).

Subjects/Keywords: heteroplasmy; fusion; fission; blood; inheritance; model; morphology; mtDNA; stem cells; segregation; oogenesis; ageing; mutations

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rajasimha, H. K. (2007). Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/29961

Chicago Manual of Style (16^th Edition):

Rajasimha, Harsha Karur. “Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation.” 2007. Doctoral Dissertation, Virginia Tech. Accessed January 22, 2021. http://hdl.handle.net/10919/29961.

MLA Handbook (7^th Edition):

Rajasimha, Harsha Karur. “Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation.” 2007. Web. 22 Jan 2021.

Vancouver:

Rajasimha HK. Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation. [Internet] [Doctoral dissertation]. Virginia Tech; 2007. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10919/29961.

Council of Science Editors:

Rajasimha HK. Insights Into Mitochondrial Genetic and Morphologic Dynamics Gained by Stochastic Simulation. [Doctoral Dissertation]. Virginia Tech; 2007. Available from: http://hdl.handle.net/10919/29961

Tampere University

6. Rovio, Anja. DNA Polymerase Gamma Mutations in Male Infertility and Ageing .

Degree: Lääketieteellisen teknologian instituutti - Institute of Medical Technology, 2006, Tampere University

URL: https://trepo.tuni.fi/handle/10024/67615

► Mitokondrio on solun energiaa tuottava organelli, jolla on oma genomi, mitokondriaalinen DNA (mtDNA). Mitokondrion DNA:ta monistaa yksi ainoa polymeraasi, polymeraasi gamma (POLG). Kirjallisuudessa on kuvattu… (more)

▼ Mitokondrio on solun energiaa tuottava organelli, jolla on oma genomi, mitokondriaalinen DNA (mtDNA). Mitokondrion DNA:ta monistaa yksi ainoa polymeraasi, polymeraasi gamma (POLG). Kirjallisuudessa on kuvattu jo noin 50 POLG mutaatiota eli geenivirhettä, ja jo pitkään niiden on uskottu olevan yhteydessä paitsi moniin hermosto- ja lihasrappeuma sairauksiin, myös vanhenemiseen liittyvien oireiden syntyyn. Tämän tutkimuksen ensimmäisessä osassa analysoitiin POLG:ssä olevan CAG-toistoalueen pituusvaihteluja eri väestöryhmissä, yleisimmissä mitokondriaalisissa sairauksissa ja lapsettomilla miehillä. Kaikissa tutkituissa väestöryhmissä toistoalueen pituus oli hyvin vakaa, yleisimmän alleelin sisältäessä 10 CAG-jaksoa. Myös kaikilla kädellisten ryhmillä on oma lajityypillinen, yleinen CAG-pituutensa, joka pitenee tultaessa pienistä apinoista simpanssin kautta gorillaan ja ihmiseen. Toistojakson pituus ei tavallisimmissa mitokondriaalisissa sairauksissa poikennut kontrolliväestöstä. Sen sijaan havaittiin, että noin 10%:lla lapsettomista miehistä puuttuu tämä ns. yleinen alleeli, kun taas tunnetusti fertiileillä miehillä se ei puuttunut yhdeltäkään. Näillä miehillä oli alentunut siittiöiden määrä, liikkuvuus oli huonontunut ja myös rakenteessa oli normaalia enemmän virheitä. Lapsettomilla miehillä havaittiin myös useita muita POLG mutaatioita, sekä kohonnut mtDNA:n mutaatioiden määrä. Muiden ryhmien tekemissä tutkimuksissa on havaittu, että näitä pariskuntia voidaan auttaa saamaan lapsi ICSI-tekniikalla, jossa siittiö viedään neulalla munasolun sisään. POLG toistoalueen pituutta kannattaisikin käyttää yhtenä kriteerinä hoitokeinoja mietittäessä niissä tapauksissa, joissa mitään muuta syytä lapsettomuuteen ei tiedetä. Tutkimuksen toinen osa keskittyi mtDNA:n mutaatioiden osuuteen vanhenemisessa. Vanhoilla ihmisillä on havaittu olevan enemmän mtDNA mutaatioita kuin nuorilla. Tämän uskotaan johtavan lisääntyneeseen happiradikaalien muodostumiseen solussa ja edelleen lisäävän mtDNA:n mutaatioiden määrää. Teoriaa testattiin Tukholmassa tehdyllä koemallilla, jossa POLG-entsyymissä oleva mtDNA:n korjausaktiivisuus turmeltiin mutaatiolla, ja tämä vioitettu "mutaattori" geeni vietiin hiireen. Mutaattorihiiret syntyivät normaaleina, mutta alkoivat jo puolen vuoden iässä vanheta näkyvästi. Niillä oli mm. osteoporoosia, kyttyräselkä, hiustenlähtöä, anemiaa, selkeää painonpudotusta, sydänsairauden ja hermoston rappeutumisen merkkejä. Sekä koirailla että naarailla oli enneaikaista hedelmättömyyttä. Tampereella tehdyissä geneettisissä analyyseissä todettiin, että hiirten kaikkiin kudoksiin kertyi moninkertaisesti enemmän mtDNA:n mutaatioita kuin samanikäisiin verrokkihiiriin. Tämä ilmeni soluhengityksen vajavaisuutena ja vähentyneenä energiantuottona kudoksissa. Hiirillä ei kuitenkaan ilmennyt selkeästi lisääntynyttä happiradikaalien tuotantoa. Hiirten keskimääräinen elinikä oli lyhentynyt, noin 48 viikkoa, kun se vastaavilla verrokkeilla oli noin 2,5 vuotta. Mutaattorihiiri mallina osoittaa, että suuri mtDNA:n mutaatioiden määrä johtaa…

Subjects/Keywords: polymeraasi gamma ; miehen lapsettomuus ; vanheneminen ; POLG ; male infertility ; ageing ; mtDNA mutations

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rovio, A. (2006). DNA Polymerase Gamma Mutations in Male Infertility and Ageing . (Doctoral Dissertation). Tampere University. Retrieved from https://trepo.tuni.fi/handle/10024/67615

Chicago Manual of Style (16^th Edition):

Rovio, Anja. “DNA Polymerase Gamma Mutations in Male Infertility and Ageing .” 2006. Doctoral Dissertation, Tampere University. Accessed January 22, 2021. https://trepo.tuni.fi/handle/10024/67615.

MLA Handbook (7^th Edition):

Rovio, Anja. “DNA Polymerase Gamma Mutations in Male Infertility and Ageing .” 2006. Web. 22 Jan 2021.

Vancouver:

Rovio A. DNA Polymerase Gamma Mutations in Male Infertility and Ageing . [Internet] [Doctoral dissertation]. Tampere University; 2006. [cited 2021 Jan 22]. Available from: https://trepo.tuni.fi/handle/10024/67615.

Council of Science Editors:

Rovio A. DNA Polymerase Gamma Mutations in Male Infertility and Ageing . [Doctoral Dissertation]. Tampere University; 2006. Available from: https://trepo.tuni.fi/handle/10024/67615

Vanderbilt University

7. Song, Zhuo. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.

Degree: PhD, Human Genetics, 2012, Vanderbilt University

URL: http://hdl.handle.net/1803/10702

► The activity of polymerase ã (pol ã) is complicated. To understand how its kinetics values affect the final function of the pol ã, I created… (more)

Subjects/Keywords: tumor somatic mutations; targeted sequencing; NRTI; polymerase gamma; mtDNA replication

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Song, Z. (2012). Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10702

Chicago Manual of Style (16^th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/10702.

MLA Handbook (7^th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Web. 22 Jan 2021.

Vancouver:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/10702.

Council of Science Editors:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/10702

8. SURESH KUMAR POOVATHINGAL. SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY.

Degree: 2011, National University of Singapore

URL: http://scholarbank.nus.edu.sg/handle/10635/29959

Subjects/Keywords: Computational Biology; Stochastic Drift; Aging; Mitochondrial DNA(mtDNA); mtDNA Mutations.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

POOVATHINGAL, S. K. (2011). SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/29959

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

POOVATHINGAL, SURESH KUMAR. “SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY.” 2011. Thesis, National University of Singapore. Accessed January 22, 2021. http://scholarbank.nus.edu.sg/handle/10635/29959.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

POOVATHINGAL, SURESH KUMAR. “SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY.” 2011. Web. 22 Jan 2021.

Vancouver:

POOVATHINGAL SK. SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY. [Internet] [Thesis]. National University of Singapore; 2011. [cited 2021 Jan 22]. Available from: http://scholarbank.nus.edu.sg/handle/10635/29959.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

POOVATHINGAL SK. SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY. [Thesis]. National University of Singapore; 2011. Available from: http://scholarbank.nus.edu.sg/handle/10635/29959

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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