Academic literature on the topic 'Chromosomal domain'
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Journal articles on the topic "Chromosomal domain"
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Chen, Bo-Wei, Ming-Hsing Lin, Chen-Hsi Chu, Chia-En Hsu, and Yuh-Ju Sun. "Insights into ParB spreading from the complex structure of Spo0J and parS." Proceedings of the National Academy of Sciences 112, no. 21 (May 11, 2015): 6613–18. http://dx.doi.org/10.1073/pnas.1421927112.
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Spo0J (stage 0 sporulation protein J, a member of the ParB superfamily) is an essential component of the ParABS (partition system of ParA, ParB, and parS)-related bacterial chromosome segregation system. ParB (partition protein B) and its regulatory protein, ParA, act cooperatively through parS (partition S) DNA to facilitate chromosome segregation. ParB binds to chromosomal DNA at specific parS sites as well as the neighboring nonspecific DNA sites. Various ParB molecules can associate together and spread along the chromosomal DNA. ParB oligomer and parS DNA interact together to form a high-order nucleoprotein that is required for the loading of the structural maintenance of chromosomes proteins onto the chromosome for chromosomal DNA condensation. In this report, we characterized the binding of parS and Spo0J from Helicobacter pylori (HpSpo0J) and solved the crystal structure of the C-terminal domain truncated protein (Ct-HpSpo0J)-parS complex. Ct-HpSpo0J folds into an elongated structure that includes a flexible N-terminal domain for protein–protein interaction and a conserved DNA-binding domain for parS binding. Two Ct-HpSpo0J molecules bind with one parS. Ct-HpSpo0J interacts vertically and horizontally with its neighbors through the N-terminal domain to form an oligomer. These adjacent and transverse interactions are accomplished via a highly conserved arginine patch: RRLR. These interactions might be needed for molecular assembly of a high-order nucleoprotein complex and for ParB spreading. A structural model for ParB spreading and chromosomal DNA condensation that lead to chromosome segregation is proposed.
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Krasikova, Alla, and Tatiana Kulikova. "Identification of Genomic Loci Responsible for the Formation of Nuclear Domains Using Lampbrush Chromosomes." Non-Coding RNA 6, no. 1 (December 25, 2019): 1. http://dx.doi.org/10.3390/ncrna6010001.
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In the cell nuclei, various types of nuclear domains assemble as a result of transcriptional activity at specific chromosomal loci. Giant transcriptionally active lampbrush chromosomes, which form in oocyte nuclei of amphibians and birds enable the mapping of genomic sequences with high resolution and the visualization of individual transcription units. This makes avian and amphibian oocyte nuclei an advantageous model for studying locus-specific nuclear domains. We developed two strategies for identification and comprehensive analysis of the genomic loci involved in nuclear domain formation on lampbrush chromosomes. The first approach was based on the sequential FISH-mapping of BAC clones containing genomic DNA fragments with a known chromosomal position close to the locus of a nuclear domain. The second approach involved mechanical microdissection of the chromosomal region adjacent to the nuclear domain followed by the generation of FISH-probes and DNA sequencing. Furthermore, deciphering the DNA sequences from the dissected material by high throughput sequencing technologies and their mapping to the reference genome helps to identify the genomic region responsible for the formation of the nuclear domain. For those nuclear domains structured by nascent transcripts, identification of genomic loci of their formation is a crucial step in the identification of scaffold RNAs.
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Krithivas, Anita, Masahiro Fujimuro, Magdalena Weidner, David B. Young, and S. Diane Hayward. "Protein Interactions Targeting the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus to Cell Chromosomes." Journal of Virology 76, no. 22 (November 15, 2002): 11596–604. http://dx.doi.org/10.1128/jvi.76.22.11596-11604.2002.
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ABSTRACT Maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) latent infection depends on the viral episomes in the nucleus being distributed to daughter cells following cell division. The latency-associated nuclear antigen (LANA) is constitutively expressed in all KSHV-infected cells. LANA binds sequences in the terminal repeat regions of the KSHV genome and tethers the viral episomes to chromosomes. To better understand the mechanism of chromosomal tethering, we performed glutathione S-transferase (GST) affinity and yeast two-hybrid assays to identify LANA-interacting proteins with known chromosomal association. Two of the interactors were the methyl CpG binding protein MeCP2 and the 43-kDa protein DEK. The interactions of MeCP2 and DEK with LANA were confirmed by coimmunoprecipitation. The MeCP2-interacting domain was mapped to the previously described chromatin binding site in the N terminus of LANA, while the DEK-interacting domain mapped to LANA amino acids 986 to 1043 in the C terminus. LANA was unable to associate with mouse chromosomes in chromosome spreads of transfected NIH 3T3 cells. However, LANA was capable of targeting to mouse chromosomes in the presence of human MeCP2 or DEK. The data indicate that LANA is tethered to chromosomes through two independent chromatin binding domains that interact with different protein partners.
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Baxter, Michael K., Maria G. McPhillips, Keiko Ozato, and Alison A. McBride. "The Mitotic Chromosome Binding Activity of the Papillomavirus E2 Protein Correlates with Interaction with the Cellular Chromosomal Protein, Brd4." Journal of Virology 79, no. 8 (April 15, 2005): 4806–18. http://dx.doi.org/10.1128/jvi.79.8.4806-4818.2005.
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ABSTRACT The papillomavirus transcriptional activator, E2, is involved in key functions of the viral life cycle. These include transcriptional regulation, viral DNA replication, and viral genome segregation. The transactivation domain of E2 is required for each of these functions. To identify the regions of the domain that mediate binding to mitotic chromosomes, a panel of mutations has been generated and their effect on various E2 functions has been analyzed. A structural model of the bovine papillomavirus type 1 (BPV1) E2 transactivation domain was generated based on its homology with the solved structure of the human papillomavirus type 16 (HPV16) domain. This model was used to identify distinct surfaces of the domain to be targeted by point mutation to further delineate the functional region of the transactivation domain responsible for mitotic chromosome association. The mutated E2 proteins were assessed for mitotic chromosome binding and, in addition, transcriptional activation and transcriptional repression activities. Mutation of amino acids R37 and I73, which are located on a surface of the domain that in HPV16 E2 is reported to mediate self-interaction, completely eliminated mitotic chromosome binding. Mitotic chromosome binding activity was found to correlate well with the ability to interact with the cellular chromosomal associated factor Brd4, which has recently been proposed to mediate the association between BPV1 E2 and mitotic chromosomes.
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Fischer, K., P. Horrocks, M. Preuss, J. Wiesner, S. Wünsch, A. A. Camargo, and M. Lanzer. "Expression of var genes located within polymorphic subtelomeric domains of Plasmodium falciparum chromosomes." Molecular and Cellular Biology 17, no. 7 (July 1997): 3679–86. http://dx.doi.org/10.1128/mcb.17.7.3679.
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Plasmodium falciparum var genes encode a diverse family of proteins, located on the surfaces of infected erythrocytes, which are implicated in the pathology of human malaria through antigenic variation and adhesion of infected erythrocytes to the microvasculature. We have constructed a complete representative telomere-to-telomere yeast artificial chromosome (YAC) contig map of the P. falciparum chromosome 8 for studies on the chromosomal organization, distribution, and expression of var genes. Three var gene loci were identified on chromosome 8, two of which map close to the telomeres at either end of the chromosome. Analysis of the previously described chromosome 2 contig map and random P. falciparum telomeric YAC clones revealed that most, if not all, 14 P. falciparum chromosomes contain var genes in a subtelomeric location. Mapping the chromosomal location of var genes expressed in a long-term culture of the P. falciparum isolate Dd2 revealed that four of the five different expressed var genes identified map within subtelomeric locations. Expression of var genes from a chromosomal domain known for frequent rearrangements has important implications for the mechanism of var gene switching and the generation of novel antigenic and adhesive phenotypes.
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LaSalle, Janine M., and Marc Lalande. "Domain organization of allele-specific DNA replication within the GABAA receptor gene cluster." Proceedings, annual meeting, Electron Microscopy Society of America 53 (August 13, 1995): 766–67. http://dx.doi.org/10.1017/s0424820100140208.
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Parental imprinting is a gamete-specific modification that distinguishes the paternal and maternal chromosomes in higher eukaryotes, resulting in allele-specific changes in chromatin organization, transcription and replication. One example of parental imprinting in humans is revealed by two distinct genetic diseases, Prader-Willi syndrome (PWS) and Angelman syndrome (AS) which both map to chromosome 15q11-13. PWS is caused by the absence of a paternal contribution to 15q11-13, while AS results from the lack of a maternal copy of the region. Within this chromosomal subregion lies a cluster of GABAA receptor β3 and α5 subunit genes (GABRB3 and GABRA5) which are separated by about 100 kb and arranged in opposite transcritional orientations (Figure 1). Allele-specific asynchronous DNA replication has previously been found to be associated with imprinted chromosomal regions.In order to further study the association between DNA replication and imprinting, allele-specific replication was assayed by fluorescence in situ hybridization (FISH). Biotin-labeled phage probes detected by FITC hybridized to each chromosome as either a singlet (unreplicated state) or a doublet (replicated state). Cells demonstrating asynchronous replication (one singlet and one doublet) for each probe are shown in Figure 2.
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Hilliker, Arthur J. "Assaying chromosome arrangement in embryonic interphase nuclei of Drosophila melanogaster by radiation induced interchanges." Genetical Research 47, no. 1 (February 1986): 13–18. http://dx.doi.org/10.1017/s0016672300024459.
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SummaryDespite recent advances in our understanding of chromatin ultrastructure, little is known of the arrangement of chromosomes during interphase, the portion of the cell cycle associated with somatic gene transcription. An experimental procedure is described which has allowed the determination of the nature of the relative arrangement during interphase of chromosomes in a specific diploid cell type of Drosophila, the salivary gland anlage of the 10–14-h-old embryo. At this stage of development the salivary gland cells have ceased mitotic divisions. Embryos of 10–14 h in age were irradiated with 12000 rads of gamma radiation and then allowed to develop into third instar larvae. The polytene chromosomes of these larvae were examined for radiation-induced interchanges. From the distribution of observed interchanges, three major features of interphase chromosome arrangement were inferred. (1) Each euchromatic chromosomal arm occupies a specific domain within the interphase nucleus which does not appreciably overlap with those of other arms. (2) Within these chromosomal domains DNA folding is very extensive. (3) The heterochromatic regions of each chromosomal arm are sequestered from the euchromatic regions. An additional point of interest concerns the nature of the interchanges observed. No reciprocal interchanges were observed – all appeared to be partial exchanges, possibly subchromatid interchanges involving only one DNA strand from each of the two exchange sites.
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Doyle, Michael, and Michael F. Jantsch. "Distinct in vivo roles for double-stranded RNA-binding domains of the Xenopus RNA-editing enzyme ADAR1 in chromosomal targeting." Journal of Cell Biology 161, no. 2 (April 28, 2003): 309–19. http://dx.doi.org/10.1083/jcb.200301034.
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The RNA-editing enzyme adenosine deaminase that acts on RNA (ADAR1) deaminates adenosines to inosines in double-stranded RNA substrates. Currently, it is not clear how the enzyme targets and discriminates different substrates in vivo. However, it has been shown that the deaminase domain plays an important role in distinguishing various adenosines within a given substrate RNA in vitro. Previously, we could show that Xenopus ADAR1 is associated with nascent transcripts on transcriptionally active lampbrush chromosomes, indicating that initial substrate binding and possibly editing itself occurs cotranscriptionally. Here, we demonstrate that chromosomal association depends solely on the three double-stranded RNA-binding domains (dsRBDs) found in the central part of ADAR1, but not on the Z-DNA–binding domain in the NH2 terminus nor the catalytic deaminase domain in the COOH terminus of the protein. Most importantly, we show that individual dsRBDs are capable of recognizing different chromosomal sites in an apparently specific manner. Thus, our results not only prove the requirement of dsRBDs for chromosomal targeting, but also show that individual dsRBDs have distinct in vivo localization capabilities that may be important for initial substrate recognition and subsequent editing specificity.
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Riddle, Nicole C., Christopher D. Shaffer, and Sarah C. R. Elgin. "A lot about a little dot — lessons learned from Drosophila melanogaster chromosome 4This paper is one of a selection of papers published in this Special Issue, entitled 29th Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process." Biochemistry and Cell Biology 87, no. 1 (February 2009): 229–41. http://dx.doi.org/10.1139/o08-119.
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The fourth chromosome of Drosophila melanogaster has a number of unique properties that make it a convenient model for the study of chromatin structure. Only 4.2 Mb overall, the 1.2 Mb distal arm of chromosome 4 seen in polytene chromosomes combines characteristics of heterochromatin and euchromatin. This domain has a repeat density of ~35%, comparable to some pericentric chromosome regions, while maintaining a gene density similar to that of the other euchromatic chromosome arms. Studies of position-effect variegation have revealed that heterochromatic and euchromatic domains are interspersed on chromosome 4, and both cytological and biochemical studies have demonstrated that chromosome 4 is associated with heterochromatic marks, such as heterochromatin protein 1 and histone 3 lysine 9 methylation. Chromosome 4 is also marked by POF (painting-of-fourth), a chromosome 4-specific chromosomal protein, and utilizes a dedicated histone methyltransferase, EGG. Studies of chromosome 4 have helped to shape our understanding of heterochromatin domains and their establishment and maintenance. In this review, we provide a synthesis of the work to date and an outlook to the future.
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Hasanova, Aytakin. "CHARACTERIZATION OF HUMAN CHROMOSOMAL CONSTITUTIVE HETEROCHROMATIN." Gulustan-Black Sea Scientific Journal of Academic Research 53, no. 02 (April 15, 2020): 08–11. http://dx.doi.org/10.36962/gbssjar5302202008.
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Heterochromatin of centromeric chromosome regions contains late replicating, largely repetitive DNA. It is suggested that heterochromatin participates in chromosome pairing, crossing-over and in chromosome disjunction control (1,3). Centromeric heterochromatin, a variety of heterochromatin, is a tightly packed form of DNA.Centromeric heterochromatin is a constituent in the formation ofactive centromeres in most higher-order organisms; the domain exists on both mitotic and interphase chromosomes. (4,5,6,8) Centromeric heterochromatin is usually formed on alpha satellite DNA in humans; however, there have been cases where centric heterochromatin and centromeres have formed on originally euchromatin domains lacking alpha satellite DNA; this usually happens as a result of a chromosome breakage event and the formed centromere is called a neocentromere.
Dissertations / Theses on the topic "Chromosomal domain"
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Tufarelli, Cristina. "Activation and silencing of α globin expression." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365741.
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Staines, Daniel Michael. "Characterisation of the 3'-boundary of the β-globin chromosomal domain in adult chicken erythrocytes." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.625070.
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Gardiner, T. J. "Functional characterisation of an evolutionary conserved domain of non-coding Y RNA in human chromosomal DNA replication." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599307.
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In order to investigate the function of the Y RNAs, I employed a human cell-free DNA replication assay. Firstly, I used this assay to verify the original observations that showed Y RNAs to be required for human chromosomal DNA replication in vitro. I then carried out density substitution experiments to show that Y RNA mediated DNA replication in human nuclei was semi-conservative. I also used a mouse cell-free system to show that Y RNA function in DNA replication can act independently of the chemical synchronisation used to prepare human nuclei and to show that Y RNA function is conserved between mouse and man. The Y RNAs are highly conserved both in terms of sequence and structure in the vertebrates. The Y RNAs are also found in some non-vertebrate organisms such as C. elegans, B. floridae and D. radiodurans although they are not found in yeast or flies. I subsequently studied the evolutionary conservation of the Y RNAs further by using the cell free system to test the functionality of several different species’ Y RNAs. I concluded that Y RNA function is conserved throughout vertebrate evolution. RNA to promote DNA replication appeared to correlate with conserved sequence domains in the double stranded stem of the RNA. From this information I generated a library of mutant hY1 RNAs containing alterations to their sequence and structure to investigate further which domains were essential for DNA replication. Mutant Y RNA with deletions of the loop and secondary stems promoted DNA replication as efficiently as wild-type human Y1 RNA. Deletions in the upper-stem of the RNA, however, did not allow DNA replication to proceed. Further alterations to the sequence of the upper stem in most cases abrogated function in DNA replication. The upper part of this double-stranded stem of hY1 RNA was not only necessary, but also sufficient for Y RNA function in DNA replication. DNA oligonucleotides were not able to substitute for human Y RNA in vitro.
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Szabo, Quentin. "Étude du repliement tridimensionnel de la chromatine en domaines topologiques." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT064.
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Mon projet de thèse a consisté à étudier les mécanismes du repliement tridimensionnel du génome dans les cellules eucaryotes. L’organisation des chromosomes est étroitement liée à la régulation de nombreuses fonctions biologiques, telles que le contrôle de l’expression génique, la réplication de l’ADN ou encore la stabilité génomique. La méthode de « chromosome conformation capture » Hi-C, qui permet la cartographie des interactions entre régions d’ADN, a révélé que chez de nombreuses espèces, le génome est organisé en domaines enrichis en interactions chromatiniennes, les « Topologically Associating Domains » (TADs). Les TADs sont apparus être des acteurs majeurs de la régulation du génome par leur capacité à définir spatialement des domaines fonctionnels. Cependant, les méthodes de chromosome conformation capture générèrent des profils d’interactions généralement moyennés à partir d’ensemble de cellules. Déterminer la nature du repliement des TADs en cellules individuelles est donc crucial pour comprendre la relation structure-fonction de ces domaines génomiques. Au cours de ma thèse, j’ai utilisé des techniques de marquage fluorescent d'ADN combinés à de la microscopie en super-résolution afin d’étudier l’organisation des chromosomes en cellules uniques. Chez la drosophile, les TADs coïncident avec le partitionnement de la chromatine en domaines épigénétiques distincts. Nous avons pu caractériser chez cette espèce que les chromosomes sont organisés en une série d’unités discrètes qui correspondent aux TADs, reflétant l’exclusion mutuelle de régions transcriptionnellement actives et inactives. Ces résultats indiquent que les TADs de drosophile forment des domaines physiques qui caractérisent un niveau d’organisation structurale des chromosomes en cellules uniques. Chez les mammifères, la majorité des TADs est formée grâce à l’action du complexe cohésine et à la présence de la protéine CCCTC-binding factor (CTCF) à leurs frontières. L'application de l'imagerie à super-résolution dans des cellules souches embryonnaires et des cellules progénitrices neuronales de souris nous a permis de caractériser l’hétérogénéité du repliement des TAD d’une cellule à l’autre. Nous avons notamment pu observer leur organisation en sous-domaines globulaires qui semblent représenter une propriété générale du repliement de la chromatine à l’échelle de la centaine de nanomètres. De plus, nos résultats indiquent que les interactions chromatiniennes sont fortement favorisées à l’intérieur des TADs dans la majorité des cellules. La déplétion de CTCF abolie l’organisation spatiale de la fibre de chromatine associée aux TAD, soulignant le rôle de cette protéine dans la génération de barrières physiques entre TAD adjacents. Ces données démontrent que le repliement dynamique des TAD est compatible avec l'établissement d'environnements chromosomiques dans lesquels les contacts sont privilégiés, et réconcilient ainsi la nature probabiliste du repliement de la chromatine avec le rôle proposé des TAD dans la définition spatiale d’unités génomiques fonctionnellesMy thesis project consisted in studying the mechanisms of the three-dimensional genome folding in eukaryotic cells. The organization of chromosomes is closely related to the regulation of many biological processes, such as gene expression control, DNA replication or genomic stability. The Hi-C "chromosome conformation capture" method, which allows the mapping of interactions between DNA regions, has revealed that the genome of many species is organized into domains enriched in chromatin interactions, the "Topologically Associating Domains" (TADs). TADs have emerged as major players of genome regulation by their ability to spatially define functional domains. However, chromosome conformation capture methods generate averaged interaction profiles that generally come from an ensemble of cells. Determining the nature and the folding of TADs in individual cells is therefore crucial to better understand the structure-function relationship of these domains. During my thesis, I used a combination of fluorescent DNA labeling and super-resolution microscopy to characterize the organization of chromosomes in single cells. In Drosophila, TADs coincide with the partitioning of the chromatin into distinct epigenetic domains. In this species, we could characterize the folding of the chromosomes into a series of discrete units that correspond to TADs, reflecting the mutual exclusion of transcriptionally active and inactive regions. These results indicate that Drosophila TADs form physical domains that characterize a higher-order layer of chromosome folding in individual cells. In mammals, the majority of TADs emerge through the action of the cohesin complex and the CCCTC-binding factor (CTCF) bound at their borders. The application of super-resolution imaging in mouse embryonic stem cells and neuronal progenitor cells revealed the high degree of cell-to-cell heterogeneity of TAD folding, ranging from condensed and globular objects to dispersed and stretched conformations. We were able to observe their organization into discrete subdomains which seem to represent a general property of the folding of the chromatin fiber at the nanoscale. Furthermore, our data indicate that the physical intermingling of the chromatin is highly favored within TADs in a large majority of cells. Depletion of CTCF abolishes the TAD-dependent spatial organization of the chromatin fiber, highlighting the role of this protein in generating physical barriers between adjacent TADs. Altogether, our results demonstrate that the dynamic folding of TAD is compatible with the establishment of chromosomal environments in which contacts are privileged, and thus reconcile the probabilistic nature of chromatin folding with the proposed role of TADs in the spatial definition of functional genomic units
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Hocher, Antoine. "Exploring the plasticity of chromosomal domains upon overexpression of silencing factors in Saccharomyces cerevisiae." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066335.
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La présence de domaines chromosomiques heterochromatiniens associé à des effets de position est une propriété communes à de nombreux génomes eukaryotes. L'intensité et l'étendue de la variégation liée aux effets de position sont généralement sensibles à la dose des protéines effectrices de l'hétérochromatine. Les propriétés d'auto-propagation des complexes d'hétérochromatine a un cout, qui est la nécessité d'établir des mécanismes stoppant la propagation de la répression transcriptionelle. Cette thèse explore la dose-dépendance de l'effet de position télomérique en étudiant le complexe SIR de la levure du boulanger. La caractérisation du groupement des télomères en foyers, de la localisation de Sir3 et de la transcription dans des souches sur-exprimant Sir3 a permis d'établir l'étendue maximale des domaines silencieux présent aux subtelomeres. L'étude de jeux de données publiés a révélé que ces domaines terminent généralement au niveau de zones correspondant où les propriétés de la chromatine montrent une transition importante. Ces transitions chromatiniennes sont requises pour survivre en présence d'un excès de protéines Sir3 puisque nous avons démontré que les mutants dot1 ne survivent pas un tel excès. En outre nous avons conduit un crible génétique qui a révélé de nombreux gènes requis pour la survie en présence d'une surdose de Sir3. Ce travail caractérise la réponse du génome à une surdose d'hétérochromatine et a permis de révéler des domaines subtélomeriques associés à des propriétés chromatiniennes particulières. En conséquence nous démontrons comment l'effet de position télomerique est efficacement restreint au subtelomere chez la levureA shared property of several eukaryotic genomes is the presence of heterochromatic chromosomal domains experiencing transcriptional variegation. The intensity and the extent of position effect variegation are sensitive to the dosage of silencing effectors in many systems. The self-propagating properties of heterochromatin machineries come with a cost, which is the requirement for mechanisms preventing ectopic spreading of silencing. This thesis explores the dose-dependency of telomere position effect, using the budding yeast SIR system as a model for chromatin based heterochromatic silencing. To assess the dose-dependency of telomere position effect in budding yeast, we systematically characterized the impact of Sir3 overexpression by quantifying the clustering of telomeres, the genome wide binding of Sir3 and its impact on coding and non coding transcription. Analysis of published data sets enabled to uncover candidates potentially responsible for the limitation of subtelomeric silent domains. Our study reveals that extension of silent domains can reach saturation, associated with the anti-silencing properties of histone marks deposited by the conserved enzyme Dot1. In addition we discovered genes required for viability upon SIR3 overexpression by conducting a genetic screen. Our work describes the dynamics of the dose dependency of heterochromatin propagation in budding yeast. It uncovers previously uncharacterized discrete chromosomal domains associated with specific chromatin features and demonstrates how telomere position effect is efficiently restricted to subtelomeres by the preexisting chromatin landscape
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Ea, Vuthy. "Dynamique et organisation supérieure de la chromatine : exploration des domaines d’association topologique." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON1T024.
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La chromatine sert de support à de multiples processus biologiques, cependant son organisation spatiale diffère fortement selon l'échelle considérée. L'expression des gènes est ainsi coordonnée par des éléments régulateurs dispersés dans le génome mais capables d'interagir entre eux. Chez les métazoaires, des expériences de capture de conformation de chromosome (3C) combinées au séquençage haut-débit (Hi-C) ont permis la découverte de domaines d'association topologique (TAD), à l'échelle de la mégabase. Puisque la résolution du Hi-C reste limitée, nous avons utilisé la 3C-qPCR pour explorer, dans des cellules souches embryonnaires murines, la dynamique chromatinienne à l'intérieur de ces domaines ainsi qu'à leurs bordures. Nous identifions ainsi une modulation des fréquences de contacts, sur quelques centaines de kilobases. Cette modulation est plus ou moins importante en fonction du contenu en gènes des domaines, mais elle semble néanmoins universelle. Des modèles dérivés de la physique des polymères permettent de décrire cette modulation sous la forme d'une hélice statistique, que la chromatine adopterait en moyenne et en l'absence d'interactions spécifiques, à l'intérieur des TAD. Cette hélice reflète certaines contraintes que la chromatine subit à l'échelle supranucléosomale. Elle est très affectée par les bordures, qui bloquent la modulation, mais elle l'est beaucoup moins par le contenu en histone de liaison H1. Par ailleurs, grâce à des résultats de Hi-C à haute résolution, nous montrons que la modulation observée chez les souris n'est pas retrouvée chez la drosophile, où les caractéristiques des TAD semblent avant tout liées au paysage épigénétique local. Pour ces deux organismes, la dynamique chromatinienne à l'intérieur des domaines est donc sous le contrôle de phénomènes différentsThe chromatin hosts various biological processes. However, its organization differs considerably depending on the scale. For example, gene expression is coordinated by regulatory elements that are dispersed in the genome but that are able to interact within the tridimensional space of the nucleus. In the Metazoa, chromosome conformation capture (3C) assays combined with high-throughput sequencing (Hi-C) uncovered the existence of topologically associating domains (TADs), at the mégabase scale. Due to the limited resolution of Hi-C, we used the 3C-qPCR method to explore, in murine embryonic stem cells, the chromatin dynamics inside TADs as well as at their borders. We found that contact frequencies undergo a periodic modulation over large genomic distances (few hundred kilobases). This modulation is weaker in gene-deserts than in gene-containing domains but it seems nevertheless to be universal. Using models derived from polymer physics, we show that this modulation can be understood as a fundamental helix shape that chromatin tends to adopt statistically, when no strong locus-specific interaction takes place, within the TADs. This statistical helix reflects some constraints that the chromatin undergoes at the supranucleosomal scale. It is affected by TADs borders, which disrupt the modulation, but linker histone H1 depletion only leads to subtle changes in the helix characteristics. Furthermore, using high-resolution Hi-C data, we found that chromatin dynamics is unconstrained in Drosophila where it seems mainly linked to the local epigenetics landscape. Therefore, distinct genome organization principles govern chromatin dynamics within mouse and Drosophila topologically associating domains
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Mitra, Robi David. "Polony sequencing : DNA sequencing technology and a computational analysis reveals chromosomal domains of gene expression." Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/8797.
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Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000.Includes bibliographical references.
The first part of this thesis describes the development of polony sequencing, a sequencing technology in which DNA is cloned, amplified and sequenced in a polymer matrix. A complex library of one to ten million linear DNA molecules is amplified by performing polymerase chain reaction (PCR) in a thin polyacrylamide film poured on a glass microscope slide. The polyacrylamide matrix retards the diffusion of the DNA molecules so that each amplification product remains localized near its parent molecule. At the end of the reaction, a number of polymerase colonies, or "polonies", have formed, each one grown from a single template molecule. As many as 5 million clones can be amplified in parallel on a single slide. By including an acrydite modification at the 5' end of one of the PCR primers, the amplified DNA will be covalently attached to the polyacrylamide matrix, allowing further enzymatic manipulations to be performed on all clones simultaneously. Also described in this thesis is my progress in development of a protocol to sequence the polonies by repeated cycles of extension with fluorescent deoxynucleotide. Because polony sequencing is inherently parallel, and sub-picoliter volumes are used for each reaction, the technology should be substantially faster and cheaper than existing methods. Applications for polony sequencing such as gene expression analysis, SNP discovery, and SNP screening will also be discussed. The second part of this thesis describes a computational analysis that tests the hypothesis that chromosomal position affects gene expression. It is shown that, throughout the genome, genes lying close together on the same chromosome often show significant coexpression. This coexpression is independent of the orientation of genes to each other, but is dependent on the distance between genes. In several cases where adjacent genes show highly correlated expression, the promoter of only one of the genes contains an upstream activating sequence (UAS) known to be associated with the expression pattern. These results suggest that in certain regions of the genome a single transcription factor binding site may regulate several genes. It is also shown that evolution may take advantage of this phenomenon by keeping genes with similar functions in adjacent positions along the chromosomes. The techniques that are presented provide a computational method to delineate the locations of chromosomal domains and identify the boundary elements that flank them.
Robi David Mitra.
Ph.D.
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Lin, Shau-Ping. "Regulation of genomic imprinting at the Dlk1-Gtl2 imprinted domain on mouse chromosome 12." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616241.
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Becking, Thomas. "Impact des bactéries féminisantes du genre Wolbachia sur l'évolution des chromosomes sexuels d'isopodes terrestres." Thesis, Poitiers, 2017. http://www.theses.fr/2017POIT2299/document.
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Les Oniscidea présentent une diversité remarquable de systèmes chromosomiques de déterminisme du sexe (hétérogamétie mâle XX/XY ou hétérogamétie femelle ZW/ZZ), dont l'origine reste encore largement inconnue à ce jour. Il a été proposé que ces différents systèmes puissent être le produit de la coévolution entre les isopodes terrestres et Wolbachia, une bactérie endosymbiotique féminisante transmise verticalement par voie ovocytaire. Dans le but de caractériser l'impact de l'endosymbiose à Wolbachia sur l'évolution des mécanismes de déterminisme du sexe, nous avons utilisé une combinaison d'approches génomique, transcriptomique et d'expression de gènes. Tout d'abord, le génome de l'espèce Armadillidium nasatum (caractérisée par un système XX/XY) a été généré et ensuite annoté structurellement et fonctionnellement. A partir de ce génome, des approches de génomique comparatives ont permis la caractérisation de séquences liées au chromosomes Y, afin de mieux comprendre les processus impliqués dans la dégénérescence des gonosomes. Afin d'identifier des effecteurs liés au déterminisme ou à la différenciation du sexe, une approche par gènes candidats a permis de caractériser des gènes à domaines DM, connus pour être impliqués dans le déterminisme du sexe de nombreuses espèces, et d'en mesurer l'expression au cours du temps. Enfin, une phylogénie des Oniscidea a été réalisée en parallèle d'expériences de réversion de sexe afin d'estimer le nombre et la direction des transitions de systèmes d'hétérogamétie au cours de l'évolution des isopodes terrestres. Ces travaux contribuent à illustrer l'impact de l'endosymbiose sur l'évolution des mécanismes de déterminisme du sexe de l'hôteOniscidea show a remarkable diversity of chromosomal sex determination systems (male heterogamety XX/XY or female heterogamety ZW / ZZ). However, the origin of such diversity is still largely unknown to date. It has been proposed that these different systems may be the product of the coevolution between terrestrial isopods and Wolbachia, a feminizing endosymbiotic bacteria transmitted vertically through oocytes. In order to characterize the impact of Wolbachia endosymbiosis on the evolution of sex determination mechanisms, we used a combination of genomic, transcriptomic and gene expression approaches. First, the genome of the species Armadillidium nasatum (characterized by an XX/XY system) was generated and then structurally and functionally annotated. From this genome, a comparative genomic approach allowed us to characterize sequences Y-linked, in order to better understand the processes involved in the sex chromosome degeneration. In order to identify effectors potentially related to sex determination or differentiation, a candidate gene approach has been used to characterize DM-domain genes, known to be involved in the sex determination pathways of many species, and then to measure their expression over development. Finally, a Oniscidea phylogeny was generated in parallel with sex-reversal experiments in order to characterize the number and the direction of the transitions of heterogenetic systems during the terrestrial isopods evolution. This work emphasize the impact of endosymbiosis on the evolution of host sex determination mechanisms
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Hamperl, Stephan [Verfasser], and Joachim [Akademischer Betreuer] Griesenbeck. "Compositional and structural analysis of selected chromosomal domains from Saccharomyces cerevisiae / Stephan Hamperl. Betreuer: Joachim Griesenbeck." Regensburg : Universitätsbibliothek Regensburg, 2012. http://d-nb.info/1027850340/34.
Full textBooks on the topic "Chromosomal domain"
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Razin, Sergey V. The nuclear matrix and spatial organization of chromosomal DNA domains. New York: Springer, 1997.
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The nuclear matrix and spatial organization of chromosomal DNA domains. New York: Chapman & Hall, 1997.
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Razin, Sergey V. The nuclear matrix and spatial organization of chomosomal DNA domains. Austin, TX: R.G. Landes, 1997.
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Vadakkan, Kunjumon Ittira. Clustering of centromeric domains in cerebellar Purkinje and granule neurons is chromosome-specific and cell-type specific. 2004.
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Peñagarikano, Olga, and Daniel H. Geschwind. CNTNAP2 and Autism Spectrum Disorders. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199744312.003.0016.
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Although autism was described in the early 1940s as a disorder of affective contact (Kanner, 1943), it was not classified as a neurodevelopmental disorder with a biological basis until the early 1980s, when studies reported its high heritability (Folstein & Rutter, 1977; Ritvo et al., 1985) and co-occurrence with chromosomal abnormalities (Gillberg & Wahlstrom, 1985; Wahlström et al., 1986). Today, autism is considered a heterogeneous neurodevelopmental syndrome and therefore termed autism spectrum disorder (ASD), characterized by variable deficits in social behavior and language, restrictive interests, and repetitive behaviors. Autism spectrum disorder has an estimated prevalence of 1:150–1:200 (Centers for Disease Control and Prevention, 2007), being one of the most common childhood disorders. In addition to the core domains necessary for diagnosis, a number of other behavioral abnormalities are frequently associated with ASD, including epilepsy, sensory abnormalities, hyperactivity, motor abnormalities, sleep disturbances, and gastrointestinal symptoms (Geschwind, 2009).
Book chapters on the topic "Chromosomal domain"
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Razin, S. V. "Chromosomal DNA Loops and Domain Organization of the Eukaryotic Genome." In Genome Structure and Function, 39–56. Dordrecht: Springer Netherlands, 1997. http://dx.doi.org/10.1007/978-94-011-5550-2_2.
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Higgins, N. Patrick, Shuang Deng, Zhenhua Pang, Richard A. Stein, Keith Champion, and Dipankar Manna. "Domain Behavior and Supercoil Dynamics in Bacterial Chromosomes." In The Bacterial Chromosome, 133–53. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555817640.ch6.
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Jones, K. W., E. Olszewska, and L. Singh. "Rapidly evolving Bkm DNA is associated with hypervariable domains." In Chromosomes Today, 22–29. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-010-9166-4_3.
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Gerasimova, Tatiana I., and Victor G. Corces. "Domains and Boundaries in Chromosomes." In Results and Problems in Cell Differentiation, 229–49. Berlin, Heidelberg: Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/978-3-540-69111-2_11.
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Carone, Dawn M., and Rachel J. O’Neill. "Marsupial Centomeres and Telomeres: Dynamic Chromosome Domains." In Marsupial Genetics and Genomics, 55–73. Dordrecht: Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-90-481-9023-2_3.
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Karschau, Jens. "Actively Replicating Domains Randomly Associate into Replication Factories." In Mathematical Modelling of Chromosome Replication and Replicative Stress, 49–74. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-08861-7_3.
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Pavelka, Margit, and Jürgen Roth. "Detection of Sites of NA Replication and of Interphase Chromosome domains." In Functional Ultrastructure, 8–9. Vienna: Springer Vienna, 2010. http://dx.doi.org/10.1007/978-3-211-99390-3_5.
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Prakash, Sachin, and Nabo Kumar Chaudhury. "Dicentric Chromosome Image Classification Using Fourier Domain Based Shape Descriptors and Support Vector Machine." In Advances in Intelligent Systems and Computing, 221–27. Singapore: Springer Singapore, 2016. http://dx.doi.org/10.1007/978-981-10-2107-7_20.
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Krawczyk, Przemek M., Jan Stap, Ron A. Hoebe, Carel H. van Oven, Roland Kanaar, and Jacob A. Aten. "Analysis of the Mobility of DNA Double-Strand Break-Containing Chromosome Domains in Living Mammalian Cells." In The Nucleus, 309–20. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-59745-406-3_19.
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Wang, Renjie, Christophe Normand, and Olivier Gadal. "High-Throughput Live-Cell Microscopy Analysis of Association Between Chromosome Domains and the Nucleolus in S. cerevisiae." In The Nucleolus, 41–57. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3792-9_4.
Full textConference papers on the topic "Chromosomal domain"
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Rajapakse, Vinodh N., Wojciech Czaja, Yves G. Pommier, William C. Reinhold, and Sudhir Varma. "Predicting expression-related features of chromosomal domain organization with network-structured analysis of gene expression and chromosomal location." In the ACM Conference. New York, New York, USA: ACM Press, 2012. http://dx.doi.org/10.1145/2382936.2382965.
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Pestell, RG, G. Di Sante, A. Di Rocco, C. Pupo, M. Crosariol, P. Tompa, A. Tantos, et al. "Abstract P5-06-09: Cyclin d1 binding to chromatin and the induction of chromosomal instability requires the fuzzy domain." In Abstracts: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, Texas. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.sabcs16-p5-06-09.
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Sadler, J. Evan. "THE MOLECULAR BIOLOGY OF VON WILLEBRAND FACTOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643930.
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Human von Willebrand factor (vWF) is a plasma glycoprotein that is synthesized by endothelial cells and megakaryocytes, and perhaps by syncytiotrophoblast of placenta. The biosynthesis of vWF is very complex, involving proteolytic processing, glycosyla-tion, disulfide bond formation, and sulfation. Mature vWF consists of a single subunit of ∼ 250,000 daltons that is assembled into multimer ranging from dimers to species of over 10 million daltons. vWF performs its essential hemostatic function through several binding interactions, forming a bridge between specific receptors on the platelet surface and components of damaged vascular subendothelial connective tissue. Inherited deficiency of vWF, or von Willebrand disease (vWD), is the most common genetically transmitted bleeding disorder worldwide. The last two years has been a time of very rapid progress in understanding the molecular biology of vWF. Four research groups have independently isolated and sequenced the 9 kilobase full-length vWF cDNA. The predicted protein sequence has provided a foundation for understanding the biosynthetic processing of vWF, and has clarified the relationship between vWF and a 75-100 kilodalton plasma protein of unknown function, von Willebrand antigen II (vWAgll)/ vWAgll is co-distributed with vWF in endothelial cells and platelets, and is deficient in patients with vWD. The cDNA sequence of vWF shows that vWAgll is a rather large pro-peptide for vWF, explaining the biochemical and genetic association between the two proteins. vWF has a complex evolutionary history marked by many separate gene segment duplications. The primary structure of the protein contains four distinct types of repeated domains present in two to four copies each. Repeated domains account for over 90 percent of the protein sequence. This sequence provides a framework for ordering the functional domains that have been defined by protein chemistry methods. A tryptic peptide from the amino-terminus of vWF that overlaps domain D3 binds to factor VIII and also appears to bind to heparin. Peptides that include domain A1 bind to collagens, to heparin, and to platelet glycoprotein Ib. A second collagen binding site appears to lie within domain A3. The vWF cDNA has been expressed in heterologous cells to produce small amounts of functionally and structurally normal vWF, indicating that endothelial cells are not unique in their ability to process and assemble vWF multimers. Site-directed mutagenesis has been used to show that deletion of the propeptide of vWF prevents the formation of multimers. Cloned cDNA probes have been employed to isolate vWF genomic DNA from cosmid and λ-phage libraries, and the size of the vWF gene appears to be ∼ 150 kilobases. The vWF locus has been localized to human chromosome 12p12—pter. Several intragenic RFLPs have been characterized. With them, vWF has been placed on the human genetic linkage map as the most telomeric marker currently available for the short arm of chromosome 12. A second apparently homologous locus has been identified on chromosome 22, but the relationship of this locus to the authentic vWF gene is not yet known. The mechanism of vWD has been studied by Southern blotting of genomic DNA with cDNA probes in a few patients. Three unrelated pedigrees have been shown to have total deletions of the vWF gene as the cause of severe vWD (type III). This form of gene deletion appears to predispose to the development of inhibitory alloantibodies to vWF during therapy with cryoprecipitate. During the next several years recombinant DNA methods will continue to contribute our understanding of the evolution, biosynthesis, and structure-function relationships of vWF, as well as the mechanism of additional variants of vWD at the level of gene structure.
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Roshtkhari, M. Javan, and S. Kamaledin Setarehdan. "Linear Discriminant Analysis of the wavelet domain features for automatic classification of human chromosomes." In 2008 9th International Conference on Signal Processing (ICSP 2008). IEEE, 2008. http://dx.doi.org/10.1109/icosp.2008.4697261.
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Chapman, Colin D., Kazuhiro Saitou, and Mark J. Jakiela. "Genetic Algorithms As an Approach to Configuration and Topology Design." In ASME 1993 Design Technical Conferences. American Society of Mechanical Engineers, 1993. http://dx.doi.org/10.1115/detc1993-0338.
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Abstract The Genetic Algorithm, a search and optimization technique based on the theory of natural selection, is applied to problems of structural topology optimization. Given a structure’s boundary conditions and maximum allowable design domain, a discretized design representation is created. Populations of genetic algorithm “chromosomes” are then mapped into the design representation, creating potentially optimal structure topologies. Utilizing genetics-based operators such as crossover and mutation, generations of increasingly-desirable structure topologies are created. In this paper, the use of the genetic algorithm (GA) in structural topology optimization is presented. An overview of the genetic algorithm will describe the genetics-based representations and operators used in a typical genetic algorithm search. After defining topology optimization and its relation to the broader area of structural optimization, a review of previous research in GA-based and non-GA-based structural optimization is provided. The design representations, and methods for mapping genetic algorithm “chromosomes” into structure topology representations, are then detailed. Several examples of genetic algorithm-based structural topology optimization are provided: we address the optimization of beam cross-section topologies and cantilevered plate topologies, and we also investigate efficient techniques for using finite element analysis in a genetic algorithm-based search. Finally, a description of potential future work in genetic algorithm-based structural topology optimization is offered.
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Jericevic, Zeljko, Loris McGavran, and Louis C. Smith. "Eigenanalysis of digital images in the Fourier domain: construction of prototypes for high-resolution human chromosomes." In OE/LASE '90, 14-19 Jan., Los Angeles, CA, edited by Gary C. Salzman. SPIE, 1990. http://dx.doi.org/10.1117/12.17825.
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Steinkamp, John A., Harry A. Crissman, Bruce E. Lehnert, Nancy M. Lehnert, and Chiranjit Deka. "Frequency-domain flow cytometry: fluorescence-lifetime-based sensing technology for analyzing cells and chromosomes labeled with fluorescent probes." In BiOS '97, Part of Photonics West, edited by Richard B. Thompson. SPIE, 1997. http://dx.doi.org/10.1117/12.273538.
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Song, Jiajun, Ossama Abdelkhalik, and Shangyan Zou. "Genetic Optimization of Shape and Control of Non-Linear Wave Energy Converters." In ASME 2020 39th International Conference on Ocean, Offshore and Arctic Engineering. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/omae2020-19156.
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Abstract This paper presents an optimization approach to design ax-isymmetric wave energy converters (WECs) based on a nonlinear hydrodynamic model. This paper shows optimal nonlinear shapes of buoy can be generated by combing basic shapes in an optimal sense. The time domain non-linear Froude-Krylov force can be computed for a complex buoy shape, by adopting analytical formulas of its basic shape components. The time domain Forude-Krylov force is decomposed into its dynamic and static components, and then contribute to the calculation of the excitation force and the hydrostatic force. A non-linear control is assumed in the form of the combination of linear and nonlinear damping terms. A variable size genetic algorithm (GA) optimization tool is developed to search for the optimal buoy shape along with the optimal control coefficients simultaneously. Chromosome of the GA tool is designed to improve computational efficiency and to leverage variable size genes to search for the optimal non-linear buoy shape. Different criteria of wave energy conversion can be implemented by the variable size GA tool. Simulation results presented in this paper show that it is possible to find non-linear buoy shapes and non-linear controllers that take advantage of non-linear hydrodynamics to improve energy harvesting efficiency with out adding reactive terms to the system.
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Giannelli, B. F. "MOLECULAR GENETICS OF HAEMOPHILIA." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643981.
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Haemophilia B, an X-linked recessive disease with an incidence of 1/30,000 newborn males, is due to defects in the gene for coagulation factor IX, which is on the long am of the X chromosome at band Xq27.1. This gene consists of approximately 34 Kb and contains 8 exons which specify a mRtfc of 2803 residues coding for a protein of 415 aa preceded by a prepro signal peptide of 46 aa. Coripanson of the functional domains of the factor IX protein with the exon structure of the gene supports the exon/protein domain hypothesis of gene evolution. The factor IX gene seems to be formed by a number of functionally and evolutionally independent modules. The signal peptide and the gla (γcarboxy-glutamic) region encoded in the first three exons are homologous to those of factor X, protein C and prothrombin. Thevfourth and fifth exons which code for the connecting peptide are homologous to one another and to the epidermal growth factor, a module that has been used in the construction of a great variety of proteins including different members of the coagulation and fibrinolytic pathways. The sixth exon encodes the activation peptide region, while the catalytic region of factor IX is coded by the seventh and eighth exon. This is at variance with other serine protease genes that have different exons for the segments containing the cardinal ami no-acids of the active centre (histidine, aspartic acid and serine).Natural selection acts against detrimental mutations of the factor IX gene and at each generation a proportion of haemophilia B genes is eliminated, as a significant number of patients does not reproduce. There appears to be no selective advantage to the heterozygote and therefore haemophilia B is maintained in the population by new mutations. Consequently, a significant proportion of patients should be born to non-carrier mothers, and unrelated patients should carry different gene defects, as recently verified by detailed analysis of individual haemophilia B genes.The defects of factor IX described so far comprise both point mutations and gene deletions. The latter affect either part or the whole of the gene and are often associated with the development of antibodies against therapeutically adninistered factor IX (the inhibitor complication). Since gene deletions may result in the complete absenceof factor IX synthesis or in the production of an extremely abnormal product, it has been suggested that mutationspreventing the synthesis of a factor IX gene product capable of inducing immune tolerance to normal factor IX is important in predisposing to the inhibitor complication.Among the point mutations described so far, those affecting the signal peptide are of particular interest. Substitutions of the arginine at positions -4 and -1 cause failure of propeptide cleavage. Thus they indicate that the propeptide consists of 18 aa an(lthat lts excision is necessary for factor IX function. It appears also that the propeptide contains a signal for γcarboxylation which has been conserved during the evolution of different γcarboxylated proteins.In spite of coagulant treatment, haemophilia B is a serious disease and one for which genetic counselling is required. Paramount for this is the detection of carriers and the diagnosis ofaffected male fetuses. DNA probes derived from the cloned factor IX gene have been used for this purpose. Carrier and first or second trimester prenatal diagnoses have been done using factors IX gene markers to follow the transmission of haemophilia B genes. Six sequence variations causing restriction fragment length polymorphisms (RFLP) in the factor IX gene have been detected and used as markers for such indirect diagnoses The efficiency of the above markers is reduced by linkage disequilibrium but, nevertheless, they offer definite carrier and nremtal diagnoses in 75-80% of the relatives of familial cases of haemophilia B.The indirect detection of gene defects is of modest help in the counselling of individuals from the families of isolated patients, but new methods for the direct detection of gene mutations promise better results in such families and also the attainment of % diagnostic success in relatives of familial cases.Finally the successful expression of recombinant factor IX genes in tissue culture and transgenic mammals raises hopes of therapeutic advances.