subject:(MtDNA mutations)

1. 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 March 08, 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. 08 Mar 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 Mar 08]. 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

2. 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 March 08, 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. 08 Mar 2021.

Vancouver:

POOVATHINGAL SK. SYSTEMS BIOLOGY OF AGING: MODELING & ANALYSIS OF MITOCHONDRIAL GENOME INTEGRITY. [Internet] [Thesis]. National University of Singapore; 2011. [cited 2021 Mar 08]. 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

Brigham Young University

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

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 March 08, 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. 08 Mar 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 Mar 08]. 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

Tampere University

4. 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 March 08, 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. 08 Mar 2021.

Vancouver:

Rovio A. DNA Polymerase Gamma Mutations in Male Infertility and Ageing . [Internet] [Doctoral dissertation]. Tampere University; 2006. [cited 2021 Mar 08]. 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

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