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Heurteau, Alexandre. "Etude bioinformatique intégrative : déterminants et dynamique des interactions chromosomiques à longue distance." Electronic Thesis or Diss., Toulouse 3, 2019. http://www.theses.fr/2019TOU30343.
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Les protéines se liants aux insulateurs (IBPs) seraient impliquées dans la structuration tri-dimensionnelle des génomes en domaines topologiques (ou " TADs). Les TADs contribueraient notamment à séparer les compartiments inactifs/hétérochromatine et actifs/euchromatine. Les IBPs sont également capables de bloquer les contacts spécifiques entre les éléments activateurs ou "enhancers" d'un TAD et les promoteurs de gènes cibles présents dans un autre TAD. Ainsi, les insulateurs influenceraient l'expression des gènes selon plusieurs modes de régulations qui reste à être caractérisés à l'échelle du génome. Les résultats obtenus dans la première partie de ma thèse montrent comment les IBPs influenceraient l'expression des gènes selon un nouveau mécanisme de régulation, comme montré à l'échelle du génome de la Drosophile. Nos analyses bioinformatiques montrent que les IBPs régulent l'étalement de l'hétérochromatine répressive (H3K27me3) à la fois en cis et en trans. Les régulations en trans impliquent des boucles de chromatine entre insulateurs positionnés à la frontière de l'hétérochromatine et des insulateurs distants positionnés aux abords de gènes euchromatiniens. Ces étalements en trans conduisent à la formation de "micro-domaines" d'hétérochromatine réprimant ainsi les gènes distants. En particulier, un mutant d'insulateur qui empêche la formation de boucle diminue significativement l'établissement des micro-domaines. De plus, ces micro-domaines se formeraient au cours du développement suggérant un nouveau mécanisme insulateur-dépendant de régulation des gènes. De plus, nous un nouveau rôle de la Cohésine, un régulateur clé des boucles 3D chez l'homme, dans la régulation des ARN non codants (ncRNAs), incluant les "PROMoters uPstream Transcripts" (PROMPTs) et les enhancers RNAs (eRNAs). L'hélicase MTR4 est essentielle au contrôle de la stabilité des ARNs codants et non codants par son rôle dans les complexes nuclear-exosome targeting (NEXT) et pA-tail exosome targeting (PAXT). De manière intéressante, la déplétion de MTR4 et des sous-unités ZFC3H1 et ZCCHC8 (ou Z1 et Z8), a conduit à l'apparition de ncRNAs à l'échelle du génome. Curieusement, la cartographie des sites de liaison de MTR4 a mis en évidence que cette hélicase se lie sur des sites distants des PROMPTs. Plutôt que d'agir en cis, nos données suggèrent que la régulation des PROMPTs pourrait impliquer des contacts spécifiques à longue distance entre ces sites distants de liaison MTR4 et les promoteurs liés par Z1/Z8. Ainsi, l'intégration des données Hi-C et la détection des PROMPTS en conditions de déplétion de MTR4, Z1 ou Z8 ont souligné le rôle possible des interactions à longue distance dans la régulation des PROMPTs, depuis les sites distants MTR4. Ces travaux pourraient établir une nouvelle relation entre la structure 3D des génomes et la régulation des ARNs non codantsInsulator Binding Proteins (IBPs) could be involved in the three-dimensional folding of genomes into topological domains (or "TADs"). In particular, TADs would help to separate the inactive/heterochromatin and active/euchromatin compartments. IBPs are also able to block specific contacts between the activator or enhancer elements of one TAD and target gene promoters present in another TAD. Thus, insulators may influence gene expression according to several regulatory modes that have yet to be characterized at genome level. The results obtained in the first part of my thesis show how IBPs influence gene expression according to a new regulatory mechanism, as shown at the scale of the Drosophila genome. Our bioinformatics analyses show that IBPs regulate the spread of repressive heterochromatin (H3K27me3) both in cis and trans. Trans regulations involve chromatin loops between insulators positioned at the heterochromatin boundary and distant insulators positioned at the edges of euchromatic genes. Trans spreading leads to the formation of "micro-domains" of heterochromatin, thereby repressing distant genes. In particular, an insulator mutant that prevents loop formation significantly reduces the establishment of micro-domains. In addition, these micro-domains would be formed during development suggesting a new insulator-dependent mechanism for gene regulation. Furthermore, we could uncover a novel function of cohesion, a key regulator of 3D loops in humans, in regulating non-coding RNAs (ncRNAs), including "PROMoters uPstream Transcripts" (PROMPTs) and enhancers RNAs (eRNAs). The MTR4 helicase is essential to the control of coding and noncoding RNA stability by the human nuclear-exosome targeting (NEXT) complex and pA-tail exosome targeting (PAXT) complex. Remarkably, ncRNAs could be detected upon depletion of the Mtr4 helicase of the human NEXT complex. Moreover, depletion of additional NEXT subunits, ZFC3H1 and ZCCHC8 (or Z1 and Z8), also led to uncover ncRNAs often produced from the same loci as upon MTR4 depletion. Curiously however, mapping of Mtr4 binding sites highlighted that Mtr4 binds to sites that are distant from PROMPTs. Rather than acting in cis, our data suggest that regulation of PROMPTs could involve specific long-distance contacts between these distant MTR4 binding sites and promoters bound by Z1/Z8. As such, integration of Hi-C data together with the detection of PROMPTS upon MTR4-, Z1- or Z8- depletions highlight possible role of long-range interactions in regulating PROMPTs, from distant MTR4-bound sites. This work may establish a new relationship between the 3D structure of genomes and the regulation of ncRNAs
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Woodward, Jessica Christina. "Cell-lineage-specific chromosomal instability in condensin II mutant mice." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22921.
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In order to equally segregate their genetic material into daughter cells during mitosis, it is essential that chromosomes undergo major restructuring to facilitate compaction. However, the process of transforming diffuse, entangled interphase chromatin into discrete, highly organised chromosomal structures is extremely complex, and currently not completely understood. The complexes involved in chromatin compaction and sister chromatid decatenation in preparation for mitosis include condensins I and II. Mutations in condensin subunits have been identified in human tumours, reflecting the importance of accurate cell division in the prevention of aneuploidy and tumour formation. Most mutations described in TCGA (The Cancer Genome Atlas) and COSMIC (Catalogue of Somatic Mutations in Cancer) are missense, and therefore likely to only partially affect condensin function. Most functional genetic studies of condensin, however, have used loss of function systems, which typically cause severe chromosome segregation defects and cell death. Mice carrying global hypomorphic mutations within the kleisin subunit of the condensin II complex develop T cell lymphomas. The Caph2nes/nes mouse model is therefore a good system for understanding how condensin dysfunction can influence tumourigenesis. However, little is known about which cellular processes are affected in mutant cells before transformation. I therefore set out to use the Caph2nes/nes mouse model to study the consequences of the condensin II deficiency on cell cycle regulation in several different hematopoietic lineages. The Caph2nes/nes mice are viable and fertile, with no obvious abnormalities other than the thymus, which is drastically reduced in size. Previous studies reported greater than a hundred-fold reduction in the number of CD4+ CD8+ thymocytes. I set out to understand why the alteration of a ubiquitously expressed protein which functions in a fundamental cellular process would result in such a cell-type specific block in development. To achieve this, I investigated the possibility that condensin II is involved in interphase processes as well as in mitosis. In addition, I studied the aspects of T cell development that may make this lineage particularly vulnerable to condensin II deficiency. Finally, I carried out a preliminary investigation into the biochemical properties of the condensin complexes. During my PhD., I found strong evidence to suggest that the Caph2nes/nes T cell-specific phenotype arises due to abnormal cell division. However, I was unable to find any evidence to support the hypothesis that the phenotype is a consequence of abnormal interphase processes. Upon systematic analysis of several stages of hematopoietic differentiation, I found that at a specific stage of T cell development, the mutation results in an increased proportion of cells with abnormal ploidy, followed by a drastic reduction in cell numbers. Erythroid cells revealed a similar increase in the frequency of hyperdiploid cells, but no reduction in cell numbers. B cells and hematopoietic precursors did not reveal an increase in hyperdiploidy, or a reduction in cell numbers in wildtype relative to mutant. Subsequently, I found preliminary evidence to suggest that the T cell-specificity may be due to more rapid progression of CD4+ CD8+ T cells from S phase to M phase, relative to other hematopoietic stages. Finally, a preliminary investigation into the biochemical properties of the condensin complex revealed apparent imbalances in the expression of condensin subunits in T, B and erythroid cells. The sedimentation profile of CAP-H2 from whole-thymus extract did not exclude the possibility that condensin subunits might be forming heavier-weight complexes with non-SMC proteins. Further work must be carried out to determine whether this sedimentation pattern is unique to T cells.
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Stear, Jeffrey Hamilton. "Studies of chromosome structure and movement in C. elegans /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/5056.
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Mascarenhas, Judita. "Chromosome dynamics in Bacillus subtilis characterization of the structural maintenance of chromosomes (SMC) complex /." [S.l. : s.n.], 2004. http://archiv.ub.uni-marburg.de/diss/z2004/0125/.
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Minnen, Anita [Verfasser], and Thorsten [Akademischer Betreuer] Mascher. "Structural Maintenance of Chromosomes (SMC) localization on the Bacillus subtilis chromosome / Anita Minnen. Betreuer: Thorsten Mascher." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1101344172/34.
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Lindow, Janet C. (Janet Christine) 1974. "A role for the Bacillus subtilis Structural Maintenance of Chromosomes (BsSMC) protein in chromosome organization and compaction." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/8385.
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Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 2002.Includes bibliographical references.
All cells must compact their chromosomes in order for the DNA to fit inside the cell or nucleus. In Bacillus subtilis, and other bacteria, replication occurs simultaneously with the organization, compaction and segregation of newly duplicated chromosomal regions. My work indicates that the B. subtilis Structural Maintenance of Chromosomes (BsSMC) protein is involved in compacting and organizing the chromosome. Increasing the amount of supercoiling of DNA is a means to compact the chromosome. This thesis describes a role for BsSMC in supercoiling. I determined that BsSMC can alter the DNA topology of plasmids in vivo. There is also genetic evidence that BsSMC is involved in supercoiling. An smc null mutant is hypersensitive to inhibitors of DNA gyrase, which reduce the level of negative supercoiling in the cell. Conversely, depletion of Topoisomerase I, which increases the amount of negative supercoiling of the chromosome, partially suppresses the phenotype of an smc null mutant. These data are consistent with the model that BsSMC affects chromosome compaction by constraining positive supercoils. Interestingly, SMC-containing complexes in eukaryotes are able to constrain positive supercoils in vitro and affect chromosome architecture suggesting that there is a conserved function for SMC proteins in chromosome structure. I also determined the subcellular localization of BsSMC. I found that BsSMC is a moderately abundant protein that can bind to many regions of the chromosome. A portion of BsSMC localizes in a pattern similar to the replication machinery.
(cont.) Simultaneous localization of BsSMC and a component of the replisome revealed that they are usually in the same region of the cell but are not always colocalized. Finally, the formation of BsSMC foci is dependent on the presence of the nucleoid but not ongoing replication. I propose that BsSMC is acting to compact newly replicated DNA by affecting DNA topology and is thereby facilitating the partitioning of sister chromosomes to opposite halves of the cell.
by Janet C. Lindow.
Ph.D.
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Cinato, Elisa. "Structure et expression du gène IFNA R2 humain : identification de la deuxième chaîne du récepteur des interférons alpha/bêta." Montpellier 2, 1996. http://www.theses.fr/1996MON20042.
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Seule la premiere chaine du recepteur des ifn-alpha/beta avait ete caracterisee. Nous avons clone le gene ifnar2, qui appartient au groupe de genes de recepteurs des cytokines sur le chromosome 21 humain. Le gene ifnar2 est a l'origine de quatre messagers differents, codant pour trois proteines. Une est secretee, deux sont des proteines transmembranaires, partageant le meme domaine extracellulaire, mais avec queue cytoplasmique differente. Nous avons montre, par complementation dans les cellules humaines mutantes u5, que la proteine avec domaine intracellulaire long est un composant fonctionnel du recepteur des ifn-alpha/beta humain
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Francki, Michael G. "The midget chromosome as a model to study cereal chromosome structure /." Title page, contents and summary only, 1995. http://web4.library.adelaide.edu.au/theses/09PH/09phf823.pdf.
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Dadon, Daniel Benjamin. "3D chromosome structure and chromatin proteomics." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104174.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.Cataloged from PDF version of thesis. "May 2016."
Includes bibliographical references.
The selective interpretation of the genome through transcription enables the production of every cell type's distinct gene expression program from a common genome. Transcription takes place within, and is controlled by, highly organized three-dimensional (3D) chromosome structures. The first part of the work presented here describes the generation of 3D chromosome regulatory landscape maps of human naive and primed embryonic stem cells. To create these 3D chromosome regulatory landscape maps, genome-wide enhancer and insulator locations were mapped and then placed into a 3D interaction framework formed by cohesin-mediated 3D chromosome structures. Enhancer (H3K27ac) and insulator (CTCF) locations were mapped using ChIP-sequencing, whereas 3D chromosome structures were detected by cohesin-ChIA-PET. 3D chromosome structures connecting insulators (CTCF-CTCF loops) were shown to form topologically associating domains (TADs) and insulated neighborhoods, which were mostly preserved in the transition between naive and primed states. Insulated neighborhoods are critical for proper gene expression, and their disruption leads to the improper regulation of local gene expression. Changes in enhancer-promoter loops occurred within preserved insulated neighborhoods during cell state transition. The CTCF anchors of CTCF-CTCF loops are conserved across species and are frequently mutated in cancer cells. These 3D chromosome regulatory landscapes provide a foundation for the future investigation of the relationship between chromosome structure and gene control in human development and disease. The work presented in the second part focuses on developing an approach called "chromatin proteomic profiling" to identify protein factors associated with various active and repressed portions of the genome marked by specific histone modifications. The histone modifications assayed by chromatin proteomic profiling are associated with genomic regions where specific transcriptional activities occur, thus implicating the identified proteins in these activities. This chromatin proteomic profiling study revealed a catalog of known, implicated, and novel proteins associated with these functionally characterized genomic regions.
by Daniel Benjamin Dadon.
Ph. D.
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Croft, Jenny Anne. "Correlating mammalian chromosome structure and function." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/13491.
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The euchromatin of mammalian chromosomes is broadly divided into two types with opposing characteristics: G-bands are revealed by Giemsa staining. These bands are generally late replicating, T-rich, low in gene density and appear to have a "closed" chromatin structure. R-bands are revealed by reverse Giemsa staining. These bands are generally early replicating, GC-rich, high in gene density and appear to have a more "open" chromatin structure. These two band types are intercalated throughout the mammalian genome making comparative studies of their behaviour difficult. However, in the human genome, chromosome 18 predominantly displays the features of G-bands and chromosome 19 generally displays the features of R-bands. These chromosomes were shown to be comparable in DNA content and size at metaphase and are, thus, ideal to investigate further the apparent links between chromosome structure and function. Some models of chromosome structure suggest differences in the higher order packaging of the different band types of metaphase chromosomes. Any differences should be reflected in the overall structure of chromosomes 18 and 19. Combining fluorescence in situ hybridisation and biochemical extraction of metaphase chromosomes, I detected no significant differences in their structure. In contrast, the two chromosomes demonstrated different structural characteristics in the interphase nucleus. I found that chromosome 18 occupies a relatively condensed territory, close to the periphery of the nucleus, while chromosome 19 occupies a considerably larger territory, more centrally located. My studies of different cell types and on cells at different stages of the cell cycle suggest that these characteristics generally apply in human cells, but not in a somatic cell hybrid background. Analysis of nuclei with a reciprocal 18:19 translocation showed that the translocated segments were orientated towards the positions occupied by their structurally normal homologues. The size but not the positioning of an interphase territory appears to be dependent on transcriptional activity.
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Almuhur, Rana Ahmad Suleiman. "Integrating chromatin structure and global chromosome dynamics." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5573/.
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DNA associates with proteins to form chromatin which is essential for the compaction of the DNA into the cell nucleus and is highly dynamic in order to allow the different biological processes of the DNA to occur. Chromatin compaction is achieved at different hierarchical levels: the 10nm fibre (DNA associates to nucleosomes formed by different histones), the Higher Order Chromatin fibre and the 300 nm chromosome structures. This study has shown that both H1 and H4 histones play a crucial role in preserving meiotic as well as mitotic chromosome structure and functional genome integrity in Arabidopsis. The role of the different linker histone H1 isoforms as well as the core histone H4 in Arabidopsis thaliana was investigated using T-DNA and RNAi mutant lines which showed different meiotic defects. Chromosomal breaks as well as non-homologous connections in the h4RNAi were linked to 45S/5S rDNA disorganisation, suggesting that H4 preserves chromosome integrity at these rDNA regions. Ath1.1 mutant presented univalents and reduced chiasma frequency at metaphase I, linked to a severe defect in ASY1 localisation on the meiotic chromosome axes. Thus, indicating that histone H1.1 is vital for proper chromatin axis organization that permit normal loading of recombination machinery proteins in Arabidopsis.
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Gilbert, Sandra L. (Sandra Leigh) 1968. "Chromatin structure of the inactive X chromosome." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85344.
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Sun, Lawrence (Lawrence J. ). "Inference of 3D structure of diploid chromosomes." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/119570.
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Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 61-62).
The spatial organization of DNA in the cell nucleus plays an important role for gene regulation, DNA replication, and genomic integrity. Through the development of chromosome capture experiments (such as 3C, 4C, Hi-C) it is now possible to obtain the contact frequencies of the DNA at the whole-genome level. In this thesis, we study the problem of reconstructing the 3D organization of the genome from whole-genome contact frequencies. A standard approach is to transform the contact frequencies into noisy distance measurements and then apply semidefinite programming (SDP) formulations to obtain the 3D configurations. However, neglected in such reconstructions is the fact that most eukaryotes including humans are diploid and therefore contain two (from the available data) indistinguishable copies of each genomic locus. Due to this, the standard approach performs very poorly on diploid organisms. We prove that the 3D organization of the DNA is not identifiable from exclusively chromosome capture data for diploid organisms. In fact, there are infinitely many solutions even in the noise-free setting. We then discuss various additional biologically relevant constraints (including distances between neighboring genomic loci and to the nucleus center or higher-order interactions). Under these conditions we prove there are finitely many solutions and conjecture we in fact have identifiability. Finally, we provide SDP formulations for computing the 3D embedding of the DNA with these additional constraints and show that we can recover the true 3D embedding with high accuracy even under noise.
by Lawrence Sun.
M. Eng.
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Horsley, Sharon Wendy. "Characterisation of chromosome 16 rearrangements in patients with alpha thalassaemia." Thesis, Oxford Brookes University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325201.
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Smith, Helen. "Condensin II Regulation and Function in Polyploid and Female Meiotic Cells in Drosophila melanogaster." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/194783.
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The cell's nucleus contains DNA in the form of chromosomes, which are the hereditary content of the organism. The proper transmission of DNA from one generation to the next is critical. Along with this crucial process, cells will also need to transcribe the DNA, silence certain genes (or whole chromosomes) during development and regulate other chromosome dynamics that are still being identified. The molecular components responsible for these processes are starting to be identified. However, the regulation of these components and how they interact with each other is not well understood.The condensin complex is one component that has been identified to play a role in chromosome dynamics. Activity of the complex has been studied in vitro but in vivo activity has been difficult to measure. Similarly, understanding the regulation of the complex has been difficult given the lack of assays and that the complex is essential for cell survival. In this dissertation, I have identified and characterized a regulator of condensin II function using Drosophila melanogaster. The chromo-domain protein Mrg15 interacts with condensin II to inhibit homologous chromosome interactions.Lastly, I look at the role of condensin II in female meiosis. Meiosis involves pairing and subsequent segregation of homologous chromosomes. The process of the initial pairing has remained elusive but specialized structures have evolved to maintain this pairing. Condensin II can antagonize a basal level of homologous pairing and also removes the specialized structure that pair meiotic chromosomes. This dissertation will add to the growing knowledge of the regulation of the condensin II complex and its role in female meiosis.
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Ross, Brian Christopher. "Computational tools for modeling and measuring chromosome structure." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/79262.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2012.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 99-112).
DNA conformation within cells has many important biological implications, but there are challenges both in modeling DNA due to the need for specialized techniques, and experimentally since tracing out in vivo conformations is currently impossible. This thesis contributes two computational projects to these efforts. The first project is a set of online and offline calculators of conformational statistics using a variety of published and unpublished methods, addressing the current lack of DNA model-building tools intended for general use. The second project is a reconstructive analysis that could enable in vivo mapping of DNA conformation at high resolution with current experimental technology.
by Brian Christopher Ross.
Ph.D.
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Almagro, Sébastien. "Organisation structurale et fonctionnelle des chromosomes." Phd thesis, Université Joseph Fourier (Grenoble), 2003. http://tel.archives-ouvertes.fr/tel-00003099.
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Nous avons utilisé une technique récente de mesure d'élasticité de chromosomes mitotiques assemblés in vitro de Xénope et mis au point une technique de fonctionnalisation par anticorps de micropipettes. Nous avons confirmé que le chromosome mitotique n'était pas un objet homogène. Il est constitué de deux parties bien distinctes : une gaine molle de chromatine et une structure rigide. Nous avons identifié les protéines SMC comme actrices de ces structures rigides. Nous avons aussi montré que l'ADN et les protéines sont nécessaires au maintien de l'organisation des chromosomes alors que l'ARN ne l'est pas. Nous avons aussi étudié le paysage énergétique du chromosome, ce qui n'avait jamais été réalisé sur un objet aussi complexe. Nous proposons un modèle dynamique de formation des chromosomes dans lequel les protéines SMC agissent comme médiatrices de la forme en bâtonnet des chromosomes mitotiques et dans lequel les ions Mg++ et Ca++ jouent le rôle d'agents de
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Mc, Elligott Richard. "Structures terminale des télomères chez les mammifères." Sherbrooke : Université de Sherbrooke, 1997.
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Avelar, Ana Teresa. "Chromosomal structure: a selectable trait for evolution." Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2012. http://hdl.handle.net/10362/8576.
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Dissertation presented to obtain the Ph.D degree in Evolutionary BiologyEvolution is driven by biological diversity, which is displayed by different phenotypes. These phenotypes arise as a coordinated response to the genetic composition of each organism. Chromosomal rearrangements (CRs), such as inversions and translocations, are a type of mutation contributing both to be-tween and within species phenotypic variation. Additionally, they are a promi-nent feature of several types of cancer, in particular lymphomas. However, unlike other types of mutations, the effects of inversions and translocations have not yet been directly quantified. The objective of this thesis is to quantify the mitotic and meiotic effects of CRs and to understand if chromosomal di-versity is an important macromutation for the generation of biological diversity. Initially, we asked whether chromosomal rearrangements are a poly-morphic mutation in the fission yeast Schizosaccharomyces pombe. We found, like others, that karyotype differences are very common in S. pombe isolates in spite of nucleotide diversity of the order observed within species diversity. This fact led us to test the genetic isolation between the natural iso-lates by scoring hybrid viabilities in pairwise crosses. We found that in some cases hybrid viability was severely impaired. These results prompted us to measure the meiotic and mitotic effects of single CRs in an otherwise isogenic background.(...)
This dissertation was sponsored by Fundação para a Ciência e Tecnologia. Apoio financeiro da FCT e do FSE no âmbito do Quadro Comunitário de apoio, BD nº SFRH/BD/33214/2007.
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Riley, Anthony David. "Probing chromosome structure using multidimensional scaling of DNA contact matrices." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/7262/.
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Chromosome conformation capture technology has provided a route to studying genome structure through DNA-DNA contact-counts. An iteration of chromosome conformation capture technology is Hi-C, which provides genome wide two dimensional contact-count data. The contact-count data from Hi-C can be viewed as a proxy for distance and using some transform function can be transformed into estimated distances. These estimated distances can be fitted into Euclidean space using the statistical tools of multidimensional scaling to give estimated chromosome or genome configurations. The first part of this thesis takes the Hi-C contact-count data for Chromosome 14, transforms it into estimated distances which are fitted into Euclidean space to give an estimated chromosome configuration. Steps are also taken to pre-process the genome contact-count matrix to refine the information held within it. The pre-processed genome contact-count matrix is transformed into estimated distances, which are fitted into Euclidean space to give an estimated genome configuration. The estimated chromosome and genome configurations are investigated, to find if known features of these structures are captured through fitting the Hi-C data. The second part of this thesis simulates contact-count data from simple configurations. Using the inverse of the transform functions the distances between points in a configuration can be transformed into mean contact-counts. The mean contact-counts are perturbed using a suitable distribution function to provide perturbed contact-counts, which are transformed into perturbed distances. The perturbed distances can be fitted into Euclidean space to give a fitted configurations. The properties of the fitted configurations are investigated and compared with the original configurations, and the properties of the perturbed distances are also investigated. Then steps are taken to improve the fitted configurations using information from the properties of the perturbed distances, with the successful techniques applied to estimating the chromosome configuration.
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Nourse, Jamie. "The structure, organisation and function of dispensable chromosomes in the phytopathogenic fungus Colltotrichum Gloeosporioides /." St. Lucia, Qld, 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16086.pdf.
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Gunawardena, Shermali Dione Shiranthini Harina, and Shermali Dione Shiranthini Harina Gunawardena. "A 3-dimensional structural analysis of diploid chromosomes." Thesis, The University of Arizona, 1994. http://hdl.handle.net/10150/626984.
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In this study, we are looking at the 3-dimensional chromosome structure of interphase diploid nuclei of Drosophila melanogaster. The goal is to determine the higher order structure of interphase chromosomes in these nuclei. Higher order structures include those structures larger than the 30nm fiber. Over the years, several general models for higher order chromosome structures have been presented. We look at three popular models for the organization of chromatin during embryogenesis, as each of these models make predictions that can be tested using high resolution in situ hybridization and image processing techniques. For this study we are using
the Notch gene for in situ hybridization to embryos in cycles 10-14.Our preliminary results are inconsistent with the radial loop model. It appears that the chromatin might be arranged in folds of 30 and 10nm fibers. We also observe a difference in chromatin structure as the embryo gets older. As the Notch gene is being transcribed during cycle 14 we observe a puffing event. In this study we hope to expand on these observations and present further areas that need to be explored in order to conclusively distinguish these phenomena during early embryogenesis.
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Hemming, D. J. "An immunological study of the role of histones in lampbrush chromosome structure." Thesis, University of Liverpool, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383516.
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Johansson, Anna-Mia. "Chromosome-wide gene regulatory mechanisms in Drosophila melanogaster." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33928.
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In Drosophila there are two different chromosome-wide targeting systems, the dosage compensation system that equalizes the transcriptional output from X-linked genes between males and females, and the regulation of the 4th chromosome mediated by the POF protein. The best studied of these two mechanisms is the dosage compensation system. To attain dosage compensation in Drosophila at least five different proteins, encoded by the male-specific lethal genes msl1, msl2, msl3, mle and mof, are required. These proteins together with two non-coding RNAs (roX1 and roX2) form a dosage compensation complex (MSL complex), which binds exclusively to the X chromosome in Drosophila males and up-regulates the transcription approximately two times. In this thesis I show that roX1 and roX2 are most likely the only non-coding RNAs within the MSL complex. As expected, the roX transcripts were enriched within the MSL complex. Interestingly, one additional transcript was identified within the MSL complex. This transcript did not associate with the X chromosome and is therefore not believed to be involved in up-regulation of the X-linked genes. This transcript encodes for the rate limiting component in the MSL complex, the MSL2 protein. A model is proposed in which free, partial or complete, MSL complex feed-back regulates the amount of msl2 transcript, and thereby limits the MSL complex production. The second chromosome-wide regulatory system in flies acts on an autosome, the heterochromatic 4th chromosome. This regulation is a balancing mechanism between at least two different proteins, the chromosome 4 specific protein painting of fourth (POF) and heterochromatin protein 1 (HP1). POF binds to nascent RNAs transcribed from the 4th chromosome and HP1 target the same set of genes at the chromatin level. POF stimulates the transcribed genes, while HP1 represses them; together they create the most optimal condition for these genes. This type of balancing mechanism may be a more general way to fine-tune transcription at a chromosome-wide level and raises the question about autosomal gene regulation as a general mechanism.
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Caravaca, Guasch Juan Manuel. "Elementos estructurales de la cromatina en los cromosomas mitóticos." Doctoral thesis, Universitat Autònoma de Barcelona, 2004. http://hdl.handle.net/10803/3520.
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Nuestro grupo ha estudiado la estructura de la cromatina de núcleos de eritrocitos de pollo (Bartolomé et al., 1994; Bartolomé et al., 1995; Bermúdez et al., 1998). La consecuencia de estos estudios ha sido la elaboración de un modelo para el plegamiento de la fibra de cromatina con una elevada concentración local del DNA (Daban y Bermúdez, 1998; Daban, 2000). Sin embargo, el nivel máximo de condensación en la cromatina, se encuentra en el interior de los cromosomas metafásicos. Aunque la bibliografía ha planteado diferentes modelos para el plegamiento de la cromatina en el interior de éstos, existe un conocimiento muy escaso acerca de la estructura molecular de la cromatina en los cromosomas condensados.Se ha realizado un estudio exhaustivo de microscopía electrónica de transmisión sobre la estructura de los cromosomas metafásicos de células HeLa. Se han estudiado un total de 4410 micrografías de cromosomas metafásicos, que en su mayor parte han sido tratados con diversos medios parcialmente desnaturalizantes, para poder analizar su estructura interna.
Morfológicamente, los cromosomas estudiados en este trabajo pueden agruparse en tres tipos diferentes: compactos, granulados y fibrilados. La morfología más abundante es la compacta y se observa en presencia de cationes monovalentes y divalentes a concentración similar a la presente en la cromatina metafásica (Mg2+ 1.7-40 mM). Estos cromosomas tienen las cromátidas muy densas y en sus bordes se aprecian una serie de estructuras planas superpuestas. En condiciones de menor concentración de cationes (Mg2+£ 1.7 mM), la morfología dominante es la granular. Estos cromosomas están compuestos principalmente por gran cantidad de cuerpos circulares de 30-40 nm de diámetro. Únicamente en condiciones de fuerza iónica extremadamente baja podemos encontrar la morfología fibrilar, la cual se caracteriza por la abundancia de fibras de 30-40 nm.
Los resultados obtenidos con cromosomas parcialmente desnaturalizados nos permiten concluir que existen tres elementos estructurales en el interior de los cromosomas metafásicos: la fibra, el gránulo y la placa.
Las fibras gruesas con diámetros que oscilan entre los 100 y los 500 nm son el resultado de la deformación plástica de las cromátidas durante los diferentes procesos de preparación de las muestras. En función de las condiciones iónicas del medio las fibras gruesas muestran gránulos o placas en su interior. Las fibras delgadas están formadas por una sucesión de cuerpos de 30-40 nm de diámetro unidos irregularmente mediante interacciones cabeza-cola. Las fibras delgadas se observan dominantemente en condiciones de concentración salina extremadamente baja.
Los gránulos son unos cuerpos circulares compactos de unos 30-40 nm de diámetro. Estos cuerpos compactos descritos previamente por nuestro grupo y se interpretaron como una forma de plegamiento solenoidal de la fibra de 30 nm (Daban y Bermúdez, 1998). Se encuentran presentes en todas las condiciones estudiadas en este trabajo, siendo especialmente abundantes en presencia de iones divalentes a concentración baja y en muestras tratadas con nucleasa micrococal.
La placa es un elemento estructural característico de los cromosomas cuando éstos se encuentran en su forma más compacta, en presencia de concentraciones elevadas de cationes divalentes. Esta estructura no había sido descrita previamente por otros laboratorios. Es una estructura cromatínica de gran regularidad y con una superficie muy lisa. Hemos estimado la altura de estas placas a través de muestras sombreadas unidireccionalemente con platino. El promedio de los valores obtenidos es de 6.7 ± 1.4 nm.
En conjunto los resultados obtenidos en esta tesis permiten sugerir que el componente principal de la cromatina en los cromosomas metafásicos es el gránulo de 30-40 nm. Dependiendo de las condiciones iónicas, este elemento estructural fundamental se agrega a través de uniones cabeza-cola para formar fibras (fuerza iónica muy baja), o bien se agrega mediante interacciones laterales para formar placas (condiciones salinas próximas a las de la cromatina metafásica).
Our group has studied the chromatin structure in the chicken erythrocyte nuclei (Bartolome et al., 1994; Bartolomé et al., 1995; Bermúdez et al., 1998). The consequences of this studies has been the elaboration of a folding model of the chromatin fiber with a high local concentration of DNA. However, the maximum level of chromatin condensation, is found in the metaphase chromosomes. Although the bibliography has proposed different models to explain the chromatin folding inside the chromosomes, there is a low knowledge about the molecular structure of chromatin in the condensed chromosomes.
In this thesis, we have carried out an exhaustive electron microscopy study about the HeLa cells metaphase chromosomes. We have studied a large number of chromosome electron micrographs (4410). Chromosomes were partially denaturated under a wide variety of conditions in order to observe some chromatin structural element inside them.
Our studies indicate that chromosomes can adopt three global structural forms in function of the ionic conditions: compact, granular and fibrillar.
The compact form is the most frequent and we can observe it in the presence of monovalent and divalent cations in similar concentrations than the ones found in metaphase chromatin (Mg2+ 1.7-40 mM). These chromosomes have highly condensed chromatids and we can appreciate overlapped chromatin plates around the chromosomes edges. When the chromosomes are incubated with solutions containing lower cations concentration (Mg 2+£ 1.7 mM) they become granular. The granular structures seen inside these chromosomes show a diameter of about 35 nm. Fibrillar chromosomes are observed only at very low ionic strength. The fibers seen emanating from the chromatids have a diameter of 30-40 nm.
Our results obtained from partially denaturated chromosomes show that there are three structural elements inside the metaphase chromosomes: the fiber, the 30-40 nm chromatin granule and the plate.
The largest fibers with a diameter of 100-400 nm, presumably are produced by mechanical deformation of chromosomes during the preparation processes. Depending of the ionic conditions these fibrillar structures are composed by plates or granules. The thinnest fibers are formed by face to face association of the 30-40 nm chromatin granules. These kind of fibers are usually found only at very low ionic strength.
The chromatin granules are compact bodies with 35 nm of diameter. These compact bodies were previously described in our laboratory and were modeled as compact solenoids of nucleosomes forming (Daban and Bermúdez, 1998). They are usually seen at low divalent cation concentrations and in chromosome samples treated with micrococal nuclease.
The plate is the most frequent structural element when the chromosomes are in their compact form (high ionic strength, similar to physiological conditions). This element has not been described by any group. It is a chromatin element with a regular structure and very smooth surface. We have estimated the height of the steps between layers in unidirectional shadowing experiments. The value obtained is 6.7 ± 1.4 nm.
Our results suggest that the fundamental component inside the metaphase is the 30-40 nm chromatin granules. Depending of the ionic conditions, this basic structural element forms fibers through face to face interactions (very low ionic strength) or form plates through side to side interactions (high ionic strength similar to metaphase chromatin).
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Buitrago, Ospina Diana Camila. "Understanding the link between chromatin structure, chromosome conformation and gene regulation." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668639.
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Understanding the connection between DNA organization in the nucleus, and cell functioning is one of the most intriguing problems in biology. Although many interdisciplinary efforts have been developed for this aim, the mechanisms of DNA folding in such a large scale are largely unknown. Therefore, the complexity of genome structure requires different techniques to tackle several resolution levels.
In this thesis, several scales of genome folding are studied using theoretical methods. First, we focus on the DNA sequence dependent properties which define the propensity of specific loci to be recognized by proteins, finding that the flexibility of specific DNA sequences might explain their prevalence in the genome.
DNA sequence dependent properties are also important to define the first layer of chromatin organization: the nucleosome. Physical descriptors of the DNA sequence combined with the propensity for transcription factor binding are highly informative on the location of nucleosome depleted regions, which guide the position of +1 and –last nucleosomes, the rest of nucleosomes in the gene body being placed by statistical phasing. There is a clear correlation between transcriptional activity and nucleosome phasing at gene body, the causal relationship is transcription -> nucleosome organization rather than the opposite
A package for the comparative analysis of nucleosome organization was also developed in this thesis to quantitative predict changes in nucleosome organization occurring when perturbations are introduced to the cell.
Finally, we studied both the changes at the nucleosome level and at larger scale produced by the induction of DNA methylation on a natively unmethylated genome, developing a Hi-C based 3D model to gain insights into the chromatin rearrangements observed. We found very significant changes in chromatin structure induced by methylation, which are reflected in gene expression and cellular phenotype. Interestingly, these changes are found in a model organism that has not proteins prepared to recognize methylation, and accordingly can be assigned to intrinsic (not protein-mediated) effects of methylation.Comprender la conexión entre la organización del ADN en el núcleo y el funcionamiento celular es uno de los problemas más interesantes en biología. Aunque se han desarrollado muchos esfuerzos interdisciplinarios para esto, los mecanismos de plegamiento del ADN son en gran medida desconocidos. Por lo tanto, la complejidad de la estructura del genoma requiere diferentes técnicas para abordar varios niveles de resolución. En esta tesis, se estudian varias escalas de plegamiento del genoma utilizando métodos teóricos. Primero, nos centramos en las propiedades dependientes de la secuencia de ADN que definen la propensión de regiones específicas a ser reconocidos por las proteínas, descubriendo que la flexibilidad de ciertas secuencias de ADN podría explicar su prevalencia en el genoma. Las propiedades físicas del ADN también son importantes para definir la primera capa de organización de la cromatina: el nucleosoma. Los descriptores físicos de la secuencia de ADN combinados con la propensión a la unión de factores de transcripción son muy informativos sobre la posición de las regiones no afines a la formación de nucleosomas, que guían la posición de los nucleosomas +1 y –último, y el resto de los nucleosomas en el cuerpo del gen se coloca por posicionamiento estadístico. Adicionalmente, encontramos que existe una clara correlación entre la actividad transcripcional y la fase de nucleosomas en el cuerpo del gen. En esta tesis también se desarrolló un paquete para el análisis comparativo de la organización de nucleosomas que permite identificar cuantitativamente los cambios en el posicionamiento de los nucleosomas que ocurren cuando se introducen perturbaciones en la célula. Finalmente, estudiamos tanto los cambios a nivel de nucleosomas como a mayor escala producidos por la inducción de metilación del ADN en un genoma que originalmente no tiene metilación, desarrollando un modelo 3D basado en Hi-C para estudiar la reorganización de la cromatina. Encontramos cambios muy significativos en la estructura de la cromatina inducidos por la metilación, que se reflejan en la expresión génica y el fenotipo celular, en un organismo modelo que no tiene proteínas que reconocen la metilación y, en consecuencia, pueden deberse a los efectos intrínsecos de la metilación.
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Wallace, Julie Ann 1977. "Mitotic regulators and their effects on Drosophila : chromosome structure during development." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/31187.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005.Includes bibliographical references.
Variants of the canonical cell cycle are frequently used in nature to accomplish specific developmental goals. In one such variant, the endocycle, synthesis phase alternates with a gap phase without an intervening mitosis, producing cells that have multiple copies of the genome. These cells show diversity in their chromosome structure; at one extreme, the sister chromatids are separate (polyploid) and at the other extreme, the sisters are held together (polytene). The endocycle itself can be modified and these variations are speculated to correlate with the observed differences in chromosome structure. In this thesis, we have analyzed the contribution of mitotic regulators to the endocycle and polytene chromosome structure in Drosophila. We show that morula, a gene required for the transition from polytene to polyploid chromosome structure in Drosophila nurse cells, is a subunit of the anaphase-promoting complex/cyclosome. Increasing levels of cyclin B, a known mitotic target of the APC/C, does not alter the timing of the transition, indicating that CYCLIN B is not the only APC/C target at the polyteny-polyploidy transition. In mitosis, activity of APC/C and POLO lead to the loss of sister-chromatid cohesion and we find that mutants in polo are unable to progress through the polyteny-polyploidy transition. Finally, we find that the cohesin complex, a complex required for the physical attachment of sister chromatids in mitosis, is required for proper polytene chromosome structure in the salivary gland. These results describe a requirement for the cohesin complex in a variant of the cell cycle lacking mitosis and indicate that sister-chromatid cohesion differentiates polytene and polyploid chromosome structures.
by Julie Ann Wallace.
Ph.D.
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Cole-Showers, Curtis Lanre. "Population structure and demographics in Nigerian populations utilizing Y-chromosome markers." University of the Western Cape, 2014. http://hdl.handle.net/11394/5326.
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Philosophiae Doctor - PhDNigeria is peopled by ethnically and linguistically diverse populations of which little were known until the last few millennial. The absence of major natural geographical barrier increases the possibility of the populations being affected by the same demographic events. The aim of this thesis was to ascertain the genetic variations and demographics in five major Nigerian populations using Y-markers. This was done by determining the genetic structures of the Afro-asiatic speaking Hausa (n=78) of Northern Nigeria and the Niger Congo speaking populations of Igbo (n=119), Yoruba (n=238), Bini (n=13) and Ijaw (n=15) of Southern Nigeria all spread over 22 geographical origins and four (North, South east, south west and South south) geographical regions. They were compared with more than 2000 individuals from 46 populations of 20 other African and Middle Eastern countries, in published literature. The Scientific Working Group on DNA Analysis Methods (SWGDAM) recommended Y-Short Tandem Repeats (STRs) and nine Y-Single Nucleotide Polymorphisms (SNPs) haplogroups were typed with multiplex Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphisms (RFLP) and High Resolution Melting (HRM). Summary statistics and measures of diversity were determined. Population structure was assessed with Population Pairwise Differences, hierarchical Analysis of Molecular Variance, Multidimensional scaling and correspondence analysis plots. Mantel’s test was used to assess the correlation of genetic distances with geographic distances. Demographic inferences were assessed with lineage based Network reconstruction, Spatial autocorrelation plots, effective migrants per population and both Inter and Intra-lineages Times to the Most Recent Common Ancestor (TMRCA). The patterns of diversity of the Y-markers showed a North-South gradient and a notable sub-structure among the Hausa populations. The Niger-Congo speakers displayed rare presence of haplogroups R and E1b1b but a preponderance of E1b1a7. Overall, the Y markers showed high diversities and significant genetic sub-structure within the Hausa populations of Nigeria with stronger linguistic than geographical bias. The demographic evaluations gave credence for genetic validation of both historical records and archeological findings among these Nigerian populations. These populations showed stronger affiliations with other sub-Saharan African populations rather than with North African or Middle Eastern populations, lacking evidence for the Middle Eastern origins of the male founders of these populations. Finally, the contribution of these Nigerian dataset would greatly enhance the Africa meta-population on the YHRD with more than 274 new haplotypes of forensic estimation significance.
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Bähler, Jürg. "Meiotic chromosome structure, pairing and recombination in fission and budding yeast /." [S.l : s.n.], 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Di, Stefano Marco. "Structure and dynamics of entangled biopolymers: from knotted DNA to chromosomes." Doctoral thesis, SISSA, 2014. http://hdl.handle.net/20.500.11767/3886.
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Brinkman, Jacquelyn N. "Structure and evolution of supernumerary chromosomes in the Pacific Giant salamander Dicamptodon tenebrosus." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0028/MQ50727.pdf.
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Newman, Scott. "The structure and evolution of breast cancer genomes." Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/239397.
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Chromosome changes in the haematological malignancies, lymphomas and sarcomas are known to be important events in the evolution of these tumours as they can, for example, form fusion oncogenes or disrupt tumour suppressor genes. The recently described recurrent fusion genes in prostate and lung cancer proved to be iconic examples as they indicated that important gene fusions are found in the common epithelial cancers also. Breast cancers often display extensive structural and numerical chromosome aberration and have among the most complex karyotyes of all cancers. Genome rearrangements are potentially an important source of mutation in breast cancer but little is known about how they might contribute to this disease. My first aim was to carry out a structural survey of breast cancer cell line genomes in order to find genes that were disrupted by chromosome aberrations in 'typical' breast cancers. I investigated three breast cancer cell lines, HCC1187, VP229 and VP267 using data from array painting, SNP6 array CGH, molecular cytogenetics and massively parallel paired end sequencing. I then used these structural genomic maps to predict fusion transcripts and demonstrated expression of five fusion transcripts in HCC1187, three in VP229 and four inVP267. Even though chromosome aberrations disrupt and fuse many genes in individual breast cancers, a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. For example, chromosome instability might arise early and be essential to tumour suppressor loss and fusion gene formation or be a late event contributing little to cancer development. To address this question, I considered the evolution of these highly rearranged breast cancer karyotypes. The VP229 and VP267 cell lines were derived from the same patient before and after therapy-resistant relapse, so any chromosome aberration found in both cell lines was probably found in the common in vivo ancestor of the two cell lines. A large majority of structural variants detected by massively parallel paired end sequencing, including three fusion transcripts, were found in both cell lines, and therefore, in the common ancestor. This probably means that the bulk of genome rearrangement pre-dated the relapse. For HCC1187, I classified most of its mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome-endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided between earlier and later, implying that genetic instability was relatively constant throughout the evolution of the tumour. Surprisingly, the great majority of inactivating mutations and expressed gene fusions happened earlier. The non-random timing of these events suggests many were selected.
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BARRETO, L. M. "Estudos Citogenéticos em Dorstenia L. (Moraceae)." Universidade Federal do Espírito Santo, 2016. http://repositorio.ufes.br/handle/10/7838.
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Previous issue date: 2016-07-18Previous cytogenetic studies in Dorstenia mention that the species may have 24 to 72 chromosomes, and suggested a conserved chromosome number 2n = 32 for the Neotropic species. However, some information reported in the literature are dubious or insufficient to assess the potential of cytogenetic data to the better understand of systematics and evolution issues within this genus. Here, eight species of Neotropical Dorstenia had their karyotypes characterized, and the nuclear DNA content measured. Dorstenia bahiensis, D. cayapia, D. grazielae, D. hirta and D. turnerifolia had their karyotypes characterized and the DNA nuclear content measured for the first time. Morphological plant characters and morphometric data were submitted to cluster analysis, followed by a test of group sharpness, and ordination analysis, aiming to support the discussion about the potential of cytogenetic data to infrageneric systematic of Dorstenia. The species showed chromosome number of 2n = 32, varying in chromosomes morphology. The karyotypes least asymmetric were observed in Dorstenia elata, and the more asymmetric were registered in D. bahiensis and D. bonijesu. The 2C value ranged from 3.21 picograms (pg) D. bahiensis to 5.47 pg in D. arifolia. Morphologically similar species, like D. hirta and D. turnerifolia, grouped together based on morphometric data. The sharp groups based on morphometric data correspond to species circumscribed under the sections Dorstenia, Lecania and Emygodia, previously established based on the plant morphology. Our results supports that the chromosome number 2n = 32 is possible conserved in the Neotropical species of Dorstenia, and indicate the potential of cytogenetic data to the systematics of this genus.
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Goward, Melanie Elizabeth Anne. "Structural, functional and comparative studies of human chromosome 22q13.31." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620370.
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Capela, Delphine. "Analyse structurale du chromosome de Sinorhizobium meliloti souche 1021." Toulouse 3, 2000. http://www.theses.fr/2000TOU30111.
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Monfouilloux, Sylvaine. "Etude de la structure et de l'évolution d'une région de translocations sous télomériques chez l'homme." Rouen, 1997. http://www.theses.fr/1997ROUES065.
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Les extrémités des chromosomes comportent le télomère puis la région sous télomérique. Ces deux domaines se distinguent des autres régions chromosomiques car ils évoluent par des échanges entre les chromosomes hétérologues. Le télomère est une structure spécialisée constituant la fin des chromosomes et indispensable à leur stabilité. Il joue un rôle important dans l'organisation spatiale des chromosomes en particulier dans l'agglutination des extrémités chromosomiques en périphérie nucléaire. La région sous télomérique, adjacente au télomère est très redondante entre les chromosomes hétérologues et se termine avec les séquences uniques spécifiques à chaque chromosome. Sa fonction ainsi que sa structure ne sont pas bien connues. Plusieurs familles de séquences répétées y sont présentes. Certaines sont localisées uniquement à proximité du télomère, d'autres comme les minisatellites sont en majorité localisées dans les derniers mégabases des chromosomes. Nous avons étudié en détail une région sous télomérique présente sur une dizaine de chromosomes chez tous les individus. Nous montrons qu'elle s'est propagée par des translocations successives de domaines chromosomiques terminaux de 80 a 200 Kb, impliquant des processus de recombinaison divers. Ces translocations se sont produites après la séparation de l'homme et du chimpanzé. La stabilité de la région apparaît variable suivant les chromosomes ce qui se traduit par un polymorphisme des localisations de la région entre les individus. Cette région sous télomérique a évolué de façon très différente entre l'homme et le chimpanzé. Nous proposons que cette évolution pourrait être conditionnée par la présence de gènes adjacents à la région sous télomerique. Nous avons en effet montré que des gènes ubiquitaires se trouvent à quelques dizaines de Kb en aval de la région sous télomérique. Leur expression pourrait être influencée par la chromatine adjacente, c'est à dire par la nature de la région sous télomérique. Nous proposons enfin que l'évolution de la région sous télomérique constitue un modèle pour l'étude de l'évolution du génome humain.
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Benoist, Camille. "Intégration fonctionnelle du complexe SMC chez bacillus subtilis : étude de suppresseurs." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112268.
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Les protéines de type SMC (pour « Structural Maintenance of Chromosomes ») sont impliquées dans différents aspects de la dynamique du chromosome tels que la condensation, la ségrégation et la réparation de l’ADN. En effet, une souche de Bacillus subtilis dépourvue de SMC présente des phénotypes sévères tels qu’un défaut dans la compaction et le partitionnement du chromosome, une sensibilité accrue à certaines drogues endommageant l’ADN ainsi qu’à des inhibiteurs de gyrase. Une telle souche est incapable de croître en condition de croissance rapide. Pour comprendre l’étendue des phénotypes associés à la perte de ce gène, une identification génétique de nouveaux partenaires a été entreprise : des suppresseurs spontanés de la délétion de smc ont été isolés en condition de croissance rapide. Différentes classes de suppresseurs ont été mises en évidence, suggérant que différentes mutations pouvaient restaurer la viabilité d’une souche dépourvue de SMC. Leur caractérisation a révélé qu'ils permettaient de restaurer une partie des défauts que présente le mutant Δsmc, en particulier la résistance aux inhibiteurs de gyrase, et semblaient limiter la formation de cassures de l'ADN. Par séquençage du génome complet des suppresseurs, certaines de ces mutations ont pu être identifiées, et semblent causer une perturbation de la voie de biosynthèse des ARN de transfert. Cette perturbation permet de restaurer le défaut de croissance, et ce plus efficacement qu’une inhibition de la traduction par des drogues comme le chloramphénicol, ou par la réduction du pool de nucléotides par l’hydroxyurée. L’ensemble de ces résultats suggère que la réponse stringente pourrait être en partie responsable du phénotype suppresseur. Il est proposé qu’en dehors de la compaction du chromosome, le complexe SMC soit directement impliqué dans le maintien de l’intégrité des fourches de réplicationSMC proteins (for "Structural Maintenance of Chromosomes") are involved in different aspects of chromosome dynamic such as condensation, segregation and DNA repair. Indeed, a Bacillus subtilis mutant lacking the SMC complex shows severe phenotypes such as defects in condensation and chromosome partitioning, an increase in sensitivity DNA damaging drugs or gyrase inhibitors. The viability of such strain is limited to conditions of slow growth. To understand the range of phenotypes associated with loss of this gene, a genetic identification of new partners was undertaken: spontaneous suppressors of smc deletion were isolated in rapid growth conditions. Different classes of suppressors have been identified, suggesting that different mutations could restore the viability of a strain lacking SMC complex. Characterization of suppressors revealed they can restore some of the defects shown in Δsmc mutant, particularly resistance to gyrase inhibitors, and seemed to limit the formation of DNA breaks. By sequencing the complete genome of suppressors, some of these mutations have been identified and cause an alteration of the biosynthetic pathway of transfer RNA. This disruption can restore the growth defect more efficiently than inhibition of translation by drugs such as chloramphenicol, or by reducing the pool of nucleotides by hydroxyurea. Taken together, these results suggest that the stringent response could be partly responsible for the suppressor phenotype. It is proposed that apart from the compaction of the chromosome, the SMC complex is directly involved in maintaining the integrity of replication forks
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Dossin, François. "Mechanistic dissection of SPEN functionduring X chromosome inactivation." Thesis, Université Paris sciences et lettres, 2021. http://www.theses.fr/2021UPSLS042.
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Chez les mammifères placentaires femelles, la transcription d’un des deux chromosomes X est inactivée (ICX) au cours du développement embryonnaire. Cette inactivation est permise par Xist, un ARN non-codant qui recouvre le chromosome X à partir duquel il est exprimé, induisant ensuite l’extinction transcriptionnelle de tout ce chromosome. Les mécanismes moléculaires par lesquels Xist permet une telle répression des gènes liés à l’X demeurent globalement incompris. En 2015, la protéine SPEN a été identifiée comme interagissant directement avec l’ARN de Xist, mais sa fonction précise ainsi que son mécanisme d’action au cours de l’ICX restaient à découvrir.Au cours de mon travail de thèse, j’ai utilisé la technique du dégron inductible à l’auxine, une approche de type perte de function, permettant de dégrader SPEN à façon dans des cellules souches embryonnaires de souris (CSES) en cours d’ICX. Grâce à cette technique, je démontre que SPEN est absolument necessaire pour la repression transcriptionnelle de tout le chromosome X pendant l’ICX. Aussi, en ayant recours à des embryons de souris Spen KO, je montre que SPEN is tout autant essentiel pour l’inactivation du chromosome X paternel au cours de l’ICX soumise à empreinte. En revanche, la perte de SPEN dans des cellules différenciées, où l’ICX est déjà établie, révèle que SPEN n’est plus requis ni pour maintenir les gènes éteints, ni pour préserver l’organisation tridimensionnelle du chromosome X inactif.Par des approches de microscopie en cellules vivantes, je rapporte ensuite que SPEN est colocalisé avec l’ARN de Xist immédiatement après l’expression de ce dernier, suggérant que SPEN peut initier la répression transcriptionnelle très tôt pendand l’ICX. La caractérisation des sites de liaisons de SPEN à la chromatine révèle que SPEN est recruté uniquement au niveau des promoteurs et des enhancers des gènes actifs. Aussi, la magnitude du recrutement de SPEN aux promoteurs liés à l’X prédit la rapidité avec laquelle les gènes sont inactivés au cours de l’ICX. Enfin, une fois les genes inactivés, SPEN se dissocie de la chromatine, ce qui indique qu’une activité transcriptionnelle est requise pour l’association de SPEN à la chromatine.Par complémentation fonctionnelle, le domaine SPOC est identifié comme l’effecteur principal de l’activité répressive de SPEN pendant l’ICX, et le recrutement « forcé » de SPOC sur l’ARN de Xist suffit à entraîner l’inactivation des gènes à l’échelle du chromosome entier. L’identification de l’interactome protéique de SPOC par spectrométrie de masse révèle que SPOC interagit avec de nombreux complexes impliqués dans la répression transcriptionnelle : NCoR/SMRT (désacétylation des histones), NuRD (remodelage de la chromatine et désacétylation des histones) et la machinerie de méthylation m6A des ARN, ainsi qu’avec la machinerie de transcription (Pol2).En utilisant des approches de biophysique et de biologie structurale, je montre que SPOC interagit directement et spécifiquement avec le domaine C-terminal (CTD) de Pol2, seulement quand ce dernier est phosphorylé sur la Sérine 5. Ces résultats suggèrent que SPEN peut réprimer la transcription directement en interférant avec les évènements transcriptionnels dépendant de Pol2-CTD Ser5P.Ainsi, mon travail de these souligne l’essentialité de SPEN pour éteindre la transcription à l’échelle du chromosome X entier au cours de l’ICX, aussi bien in vitro que in vivo. Immédiatement après l’expression de Xist, SPEN est recruté aux promoteurs et enhancers de gènes actifs, réprime la transcription, puis se dissocie de la chromatin une fois les gènes éteints. Grâce à ses domaines RRMs et SPOC, SPEN joue un rôle d’intégrateur, asociant Xist à des désacétylases des histones, des remodeleurs de la chromatine, mais surtout, à la machinerie de transcriptionIn female placental mammals, dosage compensation of X-linked gene expression is achieved early during development through transcriptional inactivation of one of the two X chromosomes (XCI). This process is dependent on Xist, a long non-coding RNA which coats and silences the X chromosome from which it is transcribed. The mechanisms through which Xist initiates transcriptional silencing during XCI remain however completely unknown. In 2015, several studies identified that the SPEN protein binds Xist RNA directly, and its implication in mediating gene silencing was reported. However, its precise function and mechanism(s) of action during XCI are unclear.During my PhD, I made use of a conditional loss of function approach, the auxin inducible degron, to acutely deplete SPEN in mouse embryonic stem cells (mESCs) undergoing XCI. Using this approach, I demonstrate that SPEN is absolutely necessary for chromosome-wide Xist-mediated gene silencing during initiation of XCI. Furthermore, using conditional Spen KO mouse embryos, I show that SPEN is also required for the transcriptional inactivation of the paternal X chromosome during imprinted X inactivation. Depleting SPEN in differentiated cells, in which XCI has been established, reveals that SPEN is neither required to maintain gene silencing nor to preserve the spatial organization of the inactive X chromosome.By combining fixed and live cell imaging of Xist and SPEN, I show that SPEN colocalizes with Xist RNA, and accumulates on the X chromosome, immediately upon Xist upregulation, suggesting that SPEN can initiate gene silencing very early on during XCI. Profiling SPEN chromatin binding sites reveals that SPEN is recruited to promoters and enhancers of active genes specifically. The magnitude of SPEN recruitment to X-linked promoters dictates the efficiency with which these genes will be silenced. Remarkably, SPEN disengages from chromatin after gene silencing, indicating that active transcription required for SPEN’s association with chromatin.Using a functional complementation approach, I identify the SPOC domain as the effector of SPEN’s gene silencing activity during XCI. Artificial tethering of SPOC to Xist RNA results in transcriptional repression along the entire X chromosome, demonstrating that SPOC contains all the sufficient potential to instruct gene silencing during XCI. I further characterize the protein interactors of SPOC using mass spectrometry and reveal that SPOC interacts with several protein complexes involved in repressing transcription, including the NCoR/SMRT (histone deacetylation), the NuRD (nucleosome remodeling/histone deacetylation) and the m6A writing (governing mRNA fate) complexes. Finally, several transcription initiation and elongation factors are found to interact with SPOC, as well as the RNA polymerase II (RNAPII) transcription machinery.I identify that SPOC interacts directly and specifically with the C-terminal domain (CTD) of RNAPII only when the latter is phosphorylated on Ser5, and determine the 3D structure of the SPOC/RNAPII-CTD Ser5-P complex at 1.8Å resolution. These results suggest that SPEN could directly repress transcription during XCI by interfering with RNAPII-CTD Ser5-P templated processes.Altogether, my PhD work reveals that SPEN is essential for chromosome-wide transcriptional silencing during XCI, both in mESCs and in vivo. Following Xist upregulation, SPEN is immediately recruited to active gene promoters and enhancers, silences transcription, and subsequently disengages from chromatin. Through its RRMs and SPOC domains, SPEN acts as a molecular integrator, bridging Xist with histone deacetylases, nucleosome remodelers, RNA methyltransferases and most importantly, the transcription machinery
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Bland, Michael Jason. "Study of the constraints sustaining the two chromosome genome structure of vibrio cholerae." Paris 6, 2013. http://www.theses.fr/2013PA066794.
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The majority of bacteria have their genome organized into a single circular chromosome. These chromosomes are organized into spatially confined regions, which are characterized by having low contact frequencies between loci in different regions. These regions are formed as a result of processes related to gene transcription, chromosome replication and segregation, and replication termination and cell division. The bacterium Vibrio cholerae is among the 10% of bacteria known to have their genome divided among more than one chromosome. The two chromosomes differ in terms of replication and segregation machineries, as the second chromosome, like all bacterial secondary chromosomes, is derived from a plasmid acquired by the common ancestor of the vibrios. The structure of the chromosomes in this organism is currently unknown. This thesis details the construction of a recombination-based system designed to explore the two-chromosome genomic structure of V. Cholerae. This tool builds on a recombination system used to describe the chromosome structure of Escherichia coli, and expands its use for bacteria with multiple chromosomes, working in a manner similar to recombination cassette mediated exchange (RCME) systems. Using this tool, we demonstrate that the terminus regions of the V. Cholerae chromosomes come into physical contact with one another. This work sets the stage for a full-scale study of the V. Cholerae genomeLa majorité des bactéries ont leur génome organisé en un seul chromosome circulaire. Ces chromosomes sont organisés en régions spatialement confinés, qui sont caractérisés par des fréquences de contact faible entre les loci dans les régions différentes. Ces régions sont formées à la suite de processus liés à la transcription des gènes, la réplication et à la ségrégation des chromosomes, et la terminaison de la réplication et la division cellulaire. La bactérie Vibrio cholerae est parmi les 10 % des bactéries connues pour avoir leur génome divisé entre plusieurs chromosomes. Les deux chromosomes diffèrent en termes de mécanismes de réplication et de ségrégation, car le deuxième chromosome, comme tous les chromosomes bactériens secondaires, est dérivé d'un plasmide acquis par l'ancêtre commun des vibrions. La structure des chromosomes dans cet organisme est actuellement inconnue. Cette thèse détaille la construction d'un système basé sur la recombinaison conçu pour explorer la structure génomique de deux chromosomes de V. Cholerae. Cet outil prend appui sur un système de recombinaison utilisé pour décrire la structure du chromosome d'Escherichia coli, et son utilisation peut être élargie aux bactéries avec de multiples chromosomes, en travaillant d'une manière similaire aux systèmes de « Recombinase-mediated cassette exchange » (RMCE). En utilisant cet outil, nous démontrons que les régions terminales des chromosomes de V. Cholerae entrent en contact physique avec l'autre. Ce travail ouvre la voie à une étude à grande échelle du génome de V. Cholerae
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Wright, Matthew A. "Approaches to determining the three-dimensional structure and dynamics of bacterial chromosomes." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/33653.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Vita.
Includes bibliographical references.
The information in genomes is only partially contained in the linear sequence of their nucleotides. Their folding into dynamic three-dimensional structures creates spatial relationships between loci that likely play important functional roles. Yet so far only the broad outlines of this spatial organization have been discerned. In chapter 2 of this thesis I describe a general constraint-based framework for defining the configuration space of chromosomes. Analogous to protein structure determination through NMR, such a framework allows the quantitative reduction of the conformation space down to the level of a single structure or an ensemble of structures. It is compatible with both experimentally determined and theoretical constraints, particularly those motivated by evolutionary optimality. In chapter 3., I describe the first method to search for signals of large-scale three- dimensional structure in genome sequences. The results suggest that there is strong selection for three-dimensional relationships within the chromosome, particularly those related to transcription. The signals generated recapitulate both known structural data from microscopy and functional data on genome-wide transcription levels.
(cont.) Moreover, a detailed analysis of these signals in E. coli suggests previously unknown structural features including chromosome-long periodic looping and an axis of high transcriptional activity. There are immediate applications to other bacteria and potentially to eukaryotes.
by Matthew A. Wright.
Ph.D.
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Kabir, Sadia. "Molecular analysis of structure of chromosome 6R of triticale T701-4-6 /." Title page, summary and contents only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phk108.pdf.
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Sabir, Kenneth Spencer. "Visual Analytics Of 3D Macro Molecular Structure." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18860.
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Currently, molecular biology research is dominated by the rapid advances in DNA sequencing and related technologies. However, interpreting these data, and gaining insight into underlying molecular processes, remains challenging. Of the many strategies being pursued in this effort to understand the biomolecular machinery of life, one of the most enduring involves considering three-dimensional structure. Increasingly, experimental data is providing information on this 3D structure and dynamics of chromosomes in living cells –– these data, in turn, promise new insight into fundamental genomic processes. Similarly, the flood of DNA and protein sequence data provides a vast resource that can be used to greatly extend our ability to predict the 3D structure of proteins. In this thesis I describe Score, a visual analytics framework I have created to help biologists understand the 3D structure of chromosomes and proteins, and to explore how this structure relates to the underlying biological function. Usage of the Score framework is demonstrated through two case studies: Aquaria and Rondo. Aquaria is a web-based protein sequence structure viewer allowing users to find and navigate through structures for any given protein sequence. Rondo is a web-based chromosome structure viewer that can superimpose feature track information.
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Fielder, Anne. "A structural role for the H-NS protein in bacterial chromatin." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308709.
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Pulicani, Sylvain. "Lien entre les réarrangements chromosomiques et la structure de la chromatine chez la Drosophile." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTS105/document.
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Entre espèces, les génomes présentent des différences dans leur organisation, que ce soit au niveau du caryotype ou de l'ordre des gènes. Ceci reste vrai même entre espèces relativement proches comme l'humain et la souris, et est du aux réarrangements chromosomiques. Reconstruire l'histoire évolutive d'une lignée revient donc à déterminer des scénarios de réarrangements qui transforment un génome actuel en un autre. Le génome ancestral se trouve alors être l'un des états intermédiaires atteint par l'un de ces scénarios.Les réarrangements chromosomiques sont des évènements biologiques violents pour la cellule. En effet, de nombreux mécanismes moléculaires ont pour fonction de stopper le cycle cellulaire dans le cas où le génome aurait été altéré. De plus, les réarrangements peuvent être à l'origine de phénotypes aberrants, et donc probablement désavantageux pour leur porteur. Au vu de tout cela, il paraît raisonnable de poser l'hypothèse selon laquelle les scénarios de réarrangements sont parcimonieux.Cependant, il est admis que ce seul critère ne permet pas de reconstruire efficacement l'histoire évolutive des génomes. En effet, quelque soit le modèle utilisé pour générer les scénarios, leur nombre est exponentiel en le nombre de réarrangements. Une autre contrainte biologique doit donc être ajoutée. La conservation de la structure spatiale de la chromatine pourrait être un critère manquant essentiel. Il a été montré in vitro que lors d'une cassure double-brin suivie d'une réparation non-homologue, le brin utilisé pour la réparation se situe spatialement proche de la cassure. Notre hypothèse est donc que les points de cassures qui sont proches en 3D ont plus probablement participé à des réarrangements que les autres. Cela est appuyé par des analyses génomiques sur des cellules somatiques et entre espèces. Nommons cette hypothèse: l'hypothèse de localité.Notre approche a été de proposer une méthode pour utiliser l'information structurale afin de prioriser les scénarios de réarrangements. Les données de Hi-C ont été l'information structurale qui nous a permis d'appliquer la méthode aux scénarios entre D. melanogaster et D. yakuba.Ces résultats nous ont ensuite menés à nous demander si la structure de la chromatine ne pouvait pas elle-même évoluer. Elle serait alors susceptible d'être considérée comme un caractère phylogénétique. Cette idée est appuyée par d'autres résultats montrant la conservation de domaines topologiques entre espèces.Cette question ne semble pas avoir été posée auparavant. Elle est pourtant très intéressante car elle permet d'ouvrir tout un champ d'étude. En effet, si la structure de la chromatine porte un signal phylogénétique, alors il devient possible de s'interroger sur les mécanismes en œuvre lors de la sélection, ou sur la possibilité de reconstruire l'état ancestral de cette structure. Par la suite, il serait même possible de comparer l'évolution de la séquence et celle de la structure de la chromatine.Nous avons ainsi défini une distance entre les structures des génomes, basée sur la comparaison des contacts entre loci orthologues. Nous l'avons appliquée à une ensemble de six espèces comprenant l'humain, la souris et quatre drosophiles. Ces résultats confirment la présence d'un signal phylogénétique dans la structure spatiale des génomes. Ils mettent également en lumière l'intérêt de la mise en place de méthodes permettant de comparer efficacement des données de contacts entre espècesDifferent species have different genome organization. Whether it be the karyotype or gene order, these differences are seen even with relatively close species like Human and Mouse. This is caused by the chromosomal rearrangement. Infererence of rearrangement scenarios that transform one present-day species into another can give insight into evolutionary states, the ancestral genome being one of the intermediates of the true scenario.The chromosomal rearrangements are violent biological events for the cell. Indeed, numerous mechanisms are present to stop the cell cycle when the genome sequence is altered. Moreover, rearrangements can be the source of aberrant phenotypes, which are probably unfavorable for the carrier. With all that, it seams reasonable to assume the rearrangement scenarios are parsimonious.However, it is accepted that this criterion alone is not sufficient to efficiently build the evolutionary history of the genomes. Indeed, for whatever model we choose, the number of scenario is exponential in the number of rearrangements. Another biological constraint is needed. The spatial structure of the chromatin could be an essential missing criterion. It has been shown in vitro that when a double-stranded break of the DNA is non-homologously repaired, the strand used for repairing is close in space to the breakpoint. Our hypothesis is that the closer the breakpoints are in space, the more probable they are to participate in a rearrangement. This hold on genomics analysis of somatic cells, and between species. Let's name that hypothesis the locality hypothesis.We proposed a method to use the structural information in order to prioritize the rearrangements scenarios. The Hi-C data were the structural information that allowed us to apply our method to scenarios between D. melanogaster and D. yakuba.This results led us to ask whether the chromatin structure could evolve by itself. Then, it could be used as a phylogenetic mark. This idea is related to previous results showing the conservation of topological domains between species.This question seams to be new, and could open a new line of investigation. If the chromatin structure holds a phylogenetical signal, it becomes possible to ask ourselves about the mechanisms that occur during the selection, or if it is possible for the ancestral state to be inferred. Then, it could even be possible to compare the evolution of the sequence with the one of the chromatin structure.Thus, we defined a distance between genome structures, based on the comparison of contacts between orthologous loci. We applied this distance to a set of six species, including the Human, the Mouse and four Drosophila. This result confirms the presence of a phylogenetic signal in the spatial structure of the genomes. They also showed that we're in need for efficient methods to compare contacts data between species
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Ravel, Christophe. "Structure et dynamique du génome de Leishmania (protozoa, kinetoplastida)." Montpellier 1, 1996. http://www.theses.fr/1996MON1T004.
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Garmendia, Eva. "A Unified Multitude : Experimental Studies of Bacterial Chromosome Organization." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-332471.
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Bacteria are many, old and varied; different bacterial species have been evolving for millions of years and show many disparate life-styles and types of metabolism. Nevertheless, some of the characteristics regarding how bacteria organize their chromosomes are relatively conserved, suggesting that they might be both ancient and important, and that selective pressures inhibit their modification. This thesis aims to study some of these characteristics experimentally, assessing how changes affect bacterial growth, and how, after changing conserved features, bacteria might evolve. First, we experimentally tested what are the constraints on the horizontal transfer of a gene highly important for bacterial growth. Second, we investigated the significance of the location and orientation of a highly expressed and essential operon; and we experimentally evolved strains with suboptimal locations and orientations to assess how bacteria could adapt to these changes. Thirdly, we sought to understand the accessibility of different regions of the bacterial chromosome to engage in homologous recombination. And lastly, we constructed bacterial strains with chromosomal inversions to assess what effect the inversions had on growth rate, and how bacteria carrying costly inversions could evolve to reduce these costs. The results provide evidence for different selective forces acting to conserve these chromosome organizational traits. Accordingly, we found that evolutionary distance, functional conservation, suboptimal expression and impaired network connectivity of a gene can affect the successful transfer of genes between bacterial species. We determined that relative location of an essential and highly expressed operon is critical for supporting fast growth rate, and that its location seems to be more important than its orientation. We also found that both the location, and relative orientation of separated duplicate sequences can affect recombination rates between these sequences in different regions of the chromosome. Finally, the data suggest that the importance of having the two arms of a circular bacterial chromosome approximately equal in size is a strong selective force acting against certain type of chromosomal inversions.
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Oakey, Rebecca. "The structure of alphoid satellite DNA on normal and abnormal human Y chromosomes." Thesis, University of Oxford, 1989. http://ora.ox.ac.uk/objects/uuid:162cb1a7-3176-4b56-be8b-353b65fee236.
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The long-range structure of the Y chromosome alphoid satellite DNA has been determined in the cell lines 3E7 and OXEN. Variation in alphoid DNA block size and restriction enzyme sites were observed. The alphoid block size and restriction enzyme site variations were determined for a collection of 42 normal Y chromosomes. The alphoid DNA polymorphisms observed denned 24 Y chromosome alleles. Unexpectedly, the Y alphoid DNA alleles analysed revealed two distinct groups of Y chromosomes indicating that most of the Caucasian and Asian men analysed were descended from one of two males. The structure of the alphoid DNA was determined for 25 cell lines expected to contain abnormal Y chromosomes. Six of the cell lines lacked Y chromosomes. Four lacked both alphoid DNA and Y a centromere. 13 out of the remaining 15 Y chromosomes had centromeres and Y alphoid DNA block sizes and restriction enzyme site variation similar to that of normal Y chromosome alphoid DNA. Two of the abnormal cell lines had alphoid DNA blocks significantly different from the normal Y alphoid DNA structure. These results confirm that alphoid DNA is located very close to, or at the centromere and make it a prime candidate for a functional mammalian centromere sequence.
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Crolla, John Anthony Cesidio. "Molecular investigations of structural and numerical chromosome abnormalities in man." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241901.
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Stavrides, George Stavros. "Human chromosome 20q12-13.2 : structural, comparative and sequence variation studies." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619575.
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Mansouri, Mahmoud R. "Molecular Characterisation of Structural Chromosomal Abnormalities Associated with Congenital Disorders." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6887.
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