Dissertations / Theses on the topic 'Genetic regulation'
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1
Button, Eric A. "Regulation of T-DNA gene 7." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26177.
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The purpose of this study was two-fold. The first objective was to determine if Saccharomyces cerevisiae is a useful system for investigating the expression of T-DNA (it takes several months to obtain sufficient bacteria-free transformed plant tissue to investigate T-DNA transcription). A short fragment of T-DNA carrying T-DNA gene 7 was cloned into a yeast plasmid in an attempt to investigate the expression of gene 7 in yeast. The second objective was to determine the significance of a heat shock related sequence identified in the 5¹ region of T-DNA gene 7.
Primer extension analysis, SI nuclease mapping, and Northern hybridizations indicate that transcription of T-DNA gene 7 in yeast is different from that of transcription of gene 7 in crown gall tumors. Transcription is different because the distance between the TATA box and the transcription initiation sites must be at least 40 nucleotides in yeast. Therefore, Saccharomyces cerevisiae does not appear to be a useful system for investigating the expression of T-DNA.
Crown gall tumors were subjected to a number of stress agents, including heat shock, to determine the significance of the heat shock related sequence identified in gene 7. Primer extension analyses indicate that only cadmium and mercury have a significant effect on the expression of T-DNA gene 7. Although gene 7 responds to cadmium and mercury, the increase in transcription does not appear to be heat shock or metallothionein related, indicating that another mechanism is involved in the enhanced transcription of T-DNA gene 7 in crown gall tumors.Medicine, Faculty of
Medical Genetics, Department of
Graduate
2
Robertson, Michael Paul. "Engineered regulation of an RNA ligase ribozyme." Access restricted to users with UT Austin EID Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3035968.
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Sigvardsson, Mikael. "Regulation of immunoglobulin transcription during B-cell differentiation." Lund : Lund University, 1995. http://books.google.com/books?id=TJNqAAAAMAAJ.
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Bečanović, Kristina. "Genetic regulation of autoimmune neuroinflammation /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-726-6.
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Fouracre, Jim P. "Genetic regulation of Kranz anatomy." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:7f10306d-d942-49cd-b12f-35b29311ad3c.
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The C₄ photosynthetic cycle acts to concentrate CO₂ around the enzyme Rubisco. By doing so, C₄ photosynthesis leads to increased radiation, water and nitrogen use efficiencies. As such, C₄ photosynthesis is the most productive form of photosynthesis known. Because it enables such high levels of productivity there are large international efforts to introduce C₄ photosynthesis into non-C₄ crop species such as rice. Kranz anatomy is a characteristic leaf cellular arrangement of concentric rings of bundle sheath and mesophyll cells around closely spaced veins and is crucial to C₄ photosynthesis in almost all known examples. Despite the fact that Kranz has evolved on over 60 times independently little is known about the genetic regulation of Kranz development, as attempts to elucidate Kranz regulators using conventional mutagenesis screens have provided few insights. However, the advent of next generation DNA sequencing technologies has enabled the interrogation of genetic networks at a previously unprecedented scale. The work in this thesis describes a genome-wide transcriptomic analysis of leaf development in maize, a C₄ species, that develops both Kranz-type and non-Kranz-type leaves. Detailed bioinformatics analyses identified candidate regulators of both Kranz development and additional aspects of maize leaf development. Three of the identified Kranz candidates were functionally characterised in both C₄ and non-C₄ species. Furthermore, expression and phylogenetic analyses of GOLDEN2-LIKE (GLK) genes, a small transcription factor family previously implicated in C₄ development in maize, were extended to determine the generality of GLK function in C₄ evolution.
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Povinelli, Christine Marie. "Genetic analysis of the dihydrofolate reductase and thymidylate synthase genes of bacteriophage T4." Diss., Georgia Institute of Technology, 1987. http://hdl.handle.net/1853/25347.
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Wasinger, Valerie Christine. "Optimising gene and protein annotations and characterisation of the Mycoplasma genitalium proteome." Thesis, The University of Sydney, 1998. https://hdl.handle.net/2123/27694.
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The PROTEin complement of the genOME (proteome) can provide useful information
with respect to that obtained during the analysis of genomic DNA sequence. The proteome
has the ability to provide confirmation of the expression of genes / Open Reading Frames
(ORF’s), which can only be presumed prior to physical detection. The effects of posttranslational
modifications, and multi-gene, co-regulated and compensated pathways,
likely to contribute to debilitating disease can also be explored. Two-dimensional
electrophoresis (2-DE), the method of choice for delineation of proteomes, has been
optimised to broaden the percentage of proteome detected at any one instant. The concept
of ‘proteomic contigs’ was applied to Ochrobactrum anthropz', allowing the detection and
summation of proteins spanning the gradient pH2.3-11.0. Using the gradients pH2.3-5.0
and pH6.0-11.0, in addition to the commercially available gradient pH4.0-7.0, a total of
1158 gene-products from 6 ‘windows of protein expression’ were detected and compared
to the theoretical expression of sequenced genomes. Protein migration at the extreme basic
gradient and resolvability below IOkDa were shown to remain a challenge for 2-D
electrophoresis.
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Mauro, Vincent Peter. "Structure and regulation of nodulin genes of soybean." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75360.
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The nodulin-23 gene is an abundantly transcribed soybean gene induced in nodules during symbiosis with Rhizobium. Sequencing of the cDNA and genomic clones revealed one intron within an open reading frame. A 24,275 dalton protein was predicted. The transcription of nodulin-23 gene occurs concomitantly with Lbc$ sb3$ and nodulin-24 genes. The 5$ sp prime$-regions of nodulin-23 and Lbc$ sb3$ genes were sequenced and compared with that of nodulin-24. Three potential cis-regulatory sequences were identified. The presence of trans-acting molecule(s), possibly regulating the expression of these genes, was tested for in vitro by preincubating nuclei from embryonic axes with nodule extract and assaying for gene activation. Nodulin-23, nodulin-24, and Lbc$ sb3$ genes were specifically activated and demonstrated similar kinetics. Several genes used as controls were not stimulated. A nodule factor(s) was shown to bind the 5$ sp prime$-region of nodulin-23 gene. The corresponding DNA regions from the other two coordinately expressed nodulin genes specifically competed for this binding, whereas other genes did not bind this factor at all.
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Cleavinger, Peter Jay. "Role of the long terminal repeat in transcriptional regulation of rous sarcoma virus gene expression." free to MU campus, to others for purchase, 1996. http://wwwlib.umi.com/cr/mo/fullcit?p9841207.
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Willadsen, Kai. "Robustness in Boolean models of genetic regulatory systems /." [St. Lucia, Qld.], 2006. http://adt.library.uq.edu.au/public/adt-QU20061115.135112/index.html.
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Good, Valerie Muriel. "Genetic regulation of #gamma#-glutamyl transpeptidase." Thesis, Institute of Cancer Research (University Of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244277.
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Shar, Nisar Ahmed. "Statistical methods for predicting genetic regulation." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/16729/.
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Transcriptional regulation of gene expression is essential for cellular differentiation and function, and defects in the process are associated with cancer. Transcription is regulated by the cis-acting regulatory regions and trans-acting regulatory elements. Transcription factors bind on enhancers and repressors and form complexes by interacting with each other to control the expression of the genes. Understanding the regulation of genes would help us to understand the biological system and can be helpful in identifying therapeutic targets for diseases such as cancer. The ENCODE project has mapped binding sites of many TFs in some important cell types and this project also has mapped DNase I hypersensitivity sites across the cell types. Predicting transcription factors mutual interactions would help us in finding the potential transcription regulatory networks. Here, we have developed two methods for prediction of transcription factors mutual interactions from ENCODE ChIP-seq data, and both methods generated similar results which tell us about the accuracy of the methods. It is known that functional regions of genome are conserved and here we identified that shared/overlapping transcription factor binding sites in multiple cell types and in transcription factors pairs are more conserved than their respective non-shared/non-overlapping binding sites. It has been also studied that co-binding sites influence the expression level of genes. Most of the genes mapped to the transcription factor co-binding sites have significantly higher level of expression than those genes which were mapped to the single transcription factor bound sites. The ENCODE data suggests a very large number of potential regulatory sites across the complete genome in many cell types and methods are needed to identify those that are most relevant and to connect them to the genes that they control. A penalized regression method, LASSO was used to build correlative models, and choose two regulatory regions that are predictive of gene expression, and link them to their respective gene. Here, we show that our identified regulatory regions accumulate significant number of somatic mutations that occur in cancer cells, suggesting that their effects may drive cancer initiation and development. Harboring of somatic mutations in these identified regulatory regions is an indication of positive selection, which has been also observed in cancer related genes.
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Cholfin, Jeremy A. "Genetic regulation of prefrontal cortex development." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3251942.
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Sucic, Joseph F. "Regulation of glycogen phosphorylase genes in Dictyostelium discoideum." Diss., This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-06062008-170101/.
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關仲天 and Chung-tin Kwan. "Studies of the regulation of mouse Hoxb-3 gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31237150.
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Wong, Chi-sun, and 黃志新. "Molecular studies of the heat shock protein 60 gene of Trichinella spp(Nematoda)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31226826.
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Casey, Ryan Edward. "Mouse strain-specific splicing of Apobec3." Digital WPI, 2006. https://digitalcommons.wpi.edu/etd-theses/950.
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"Host resolution of viral infection is dependent upon components of the innate and acquired immune system. The mammalian protein Apobec3 plays an important role as part of the immune system’s innate defenses through its modification of reverse transcribed viral DNA. Recently, Apobec3 was found to directly inhibit HIV-1 and HBV replication through deaminating newly transcribed deoxycytidine residues to deoxyuridine. The ability of mouse and simian Apobec3 variants to inhibit human retroviruses and vice versa highlights the utility of analyzing cross-species homologues. To better understand this editing enzyme, differentially pathogen-susceptible inbred mice were used as an experimental model. The purpose of this project is to examine the effects of murine Apobec3 (muA3) alternative splicing on its DNA-editing characteristics. Three distinct Apobec3 isoforms were isolated from pathogen-susceptible BALB/cByJ (“Câ€) inbred mice, and two Apobec3 isoforms came from pathogen-resistant C57BL/6ByJ (“Yâ€) mice. The five muA3 isoforms were cloned, sequenced, and expressed from a constitutive promoter in a haploid Saccharomyces cerevisia strain. MuA3 DNA-editing activity was measured via the CAN1 forward mutation assay. The five isoforms studied in this project were discovered to be strain-specific. One isoform from each mouse strain mutated the yeast CAN1 locus significantly. Additionally, both muA3 isoform mRNAs derived from the pathogen-resistant Y mice were found to persist at a higher level (2.7 -12.4 fold) than any of the C mouse isoforms. This suggests that the absence of exon 5 or some other signal in the Y mice may influence transcript stability. Evidence also suggests that the murine Apobec3 start codon is actually 33bp upstream of its reference start, with implications for previous research performed using muA3. Sequencing analysis of genomic DNA revealed the presence of a 4bp insertion in a region of BALB/cByJ muA3 which may have disrupted an intronic splicing enhancer signal. Furthermore, a novel BALB/cByJ Apobec3 isoform was characterized. This is the first report of strain-specific processing with regard to muA3."
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Lee, Yiu-fai Angus, and 李耀輝. "Tissue-specific transcriptional regulation of Sox2." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3955739X.
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Lee, Yiu-fai Angus. "Tissue-specific transcriptional regulation of Sox2." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B3955739X.
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Marshall, Kristin Ann. "Group I aptazymes as genetic regulatory switches." Access restricted to users with UT Austin EID Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3034980.
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Hempel, Nadine. "Gene regulation of the human SULT1A sulfotransferases /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18151.pdf.
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呂穎怡 and Wing-yee Lui. "Regulation of junction dynamics in the testis: a new approach for male contraception." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31243447.
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Ennis, Don Gregory. "Genetics of SOS mutagenesis." Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184602.
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Previous genetic evidence suggested that RecA was required in SOS mutagenesis for its regulatory role and perhaps some other nonregulatory role (Mount, 1977; Blanco et al., 1982). I undertook a genetic study which confirmed the above studies and provided further evidence that RecA protein appeared to have a dual "role in mutagenesis; first, the cleavage of LexA repressor for the derepression of specific SOS genes and second, one or more additional role(s). For these studies a new phage mutagenesis assay was developed which allows rapid scoring of SOS mutagenesis in a large number of host mutants. I next conducted a genetic analysis to determine if the newly defined RecA mutagenesis function was separable by mutation from the numerous other phenotypes which are known to be influenced by RecA protein. From the study of recA mutants it appears that the RecA mutagenesis function(s) is genetically separable from the following RecA phenotypes: LexA cleavage, lambda cI repressor cleavage, UV resistance and homologous recombination. In addition, I discovered that the LexA cleavage function and lambda cI cleavage function is also separable. I also studied in some detail the novel genetic properties that I uncovered for recA432 mutant strains. recA432 was defined as a mutagenesis defective allele (Kato and Shinoura, 1977). LexA cleavage in recA432 cells was more easily induced that in recA⁺ cells, causing lethal filamentation of these mutant cells even at very low UV doses. I concluded that the basis for the Mut⁻ phenotype was this strain's propensity to lethally filament, which complicated the detection of mutant cells. In another set of experiments, I examined the regulatory requirements for SOS mutagenesis and Weigle phage-reactivation; I wanted to determine which SOS operons must be derepressed for this process. lexA(Ind⁻) mutant cells are defective in mutagenesis because they cannot derepress specific SOS genes required in this process. I found that the selective derepression of umuDC was sufficient to restore mutagenesis to these lexA(Ind⁻) mutants; however, derepression of umuDC and recA was required for phage reactivation.
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Werner, Maria. "Gene regulation models of viral genetic switches." Licentiate thesis, Stockholm : Datavetenskap och kommunikation, Kungliga Tekniska högskolan, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4528.
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Puckey, Loretto Helena. "The genetic regulation of lipoprotein (a) concentration." Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289825.
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Oakley, Erin J. "GENETIC REGULATION OF HEMATOPOIETIC STEM CELL AGING." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/659.
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It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. In C57BL/6 (B6) mice, the HSC population steadily increases with age, whereas in DBA/2 (D2) mice, this population declines. Our lab has previously mapped a quantitative trait locus (QTL) to murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In these dissertation studies, I first aim to characterize the congenic mouse model which was generated by introgressing D2 alleles in the QTL onto a B6 background. Using a surrogate assay to mimic aging, I analyzed the cell cycle, apoptotic and self-renewal capabilities of congenic and B6 HSCs and show that D2 alleles in the QTL affect the apoptotic and selfrenewal capabilities of HSCs. In the second aim of these studies, I used oligonucleotide arrays to compare the differential expression of B6 and congenic cells using a population enriched for primitive stem and progenitor cells. Extensive analysis of the expression arrays pointed to two strong candidates, the genes encoding Retinoblastoma like protein 1 (p107) and Sorting nexin 5 (Snx5). B6 alleles were associated with increased p107 and Snx5 expression in old HSCs therefore both genes were hypothesized to be positive regulators of stem cell number in aged mice. Finally, in the third aim of these studies, I show that the individual overexpression of p107 and Snx5 in congeic HSCs increases day35 cobblestone area forming cell (CAFC) numbers, therefore confirming their roles as positive regulators of HSC number in vitro. These studies uncover novel roles for p107 and Snx5 in the regulation of HSC numbers and provide additional clues in the complex regulation of HSC aging.
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Greenhill, Emma Rachel. "Genetic regulation of neural crest cell differentiation." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512259.
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Neural crest cells are a transient population of cells which differentiate into multiple derivatives. How these derivatives become specified is not well understood but Sox10 is known to be important in many of them. We are interested in defining the precise role of Sox10 in zebrafish melanophores. Current evidence suggests that the only vital function that Sox10 performs in melanophores is to induce expression of the melanocyte master regulator mitfa (Elworthy et al. 2003). We explored a model for Sox10 function in melanophores, based upon a model for Sox10’s role in mouse sympathetic neurons (Kim et al. 2003), and tested the following predictions: as well as inducing expression of mitfa, Sox10 will repress expression of genes downstream of Mitfa thus, Sox10 must be downregulated, via Mitfa, to allow melanophore differentiation. We observed derepression of melanophore marker genes in sox10t3 mutants, supporting the hypothesis that Sox10 represses these genes in wild type melanophores. We documented Sox10/sox10 downregulation in developing melanophores and generated transgenic lines to test whether this is necessary for differentiation. Unfortunately our experimental lines did not express our transgene so we were unable to test this hypothesis. However, transgenic lines, generated as controls, which express CFP in melanophores or xanthophores will be useful tools in their own right. Finally we conducted RNA injection experiments to explore regulation of melanophore genes by Sox10 and Mitfa. We found that injection of mitfa induces expression of all our melanophore markers whereas co-injection of mitfa and sox10 does not. We also found that the 7.2 kb sox10 promoter contains six Mitf binding sites and is Mitfa responsive. Our data broadly support our original model but also suggest that it does not describe the complete network. We propose a modified model for the role of Sox10 in the genetic regulatory network controlling melanophore development.
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Moxley, Joel Forrest. "Linking genetic regulation and the metabolic state." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/38967.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007.Includes bibliographical references (p. 257-276).
Genome sequencing and the subsequent development of high-throughput probing of cellular states have dramatically increased our ability to understand cellular compensation to perturbation. As such, integrating system-wide measurements (e.g. gene expression) with networks of protein-protein interactions and transcription factor binding has been proven as an effective means to help elucidate insights into cellular behavior. This very cellular behavior, however, is most closely linked to the metabolites and metabolic interactions occurring within the cell. Despite this fact, metabolic measurements are often given a secondary role in efforts to unravel the multi-tiered regulatory response of cells to perturbations. To begin to address this gap, we first report on the development the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software that achieve comparable throughput, effort, and cost compared with DNA arrays. Our sample workup method enables simultaneous metabolite measurements with coverage throughout central carbon metabolism and amino acid biosynthesis, using a standard Gas Chromatography Mass Spectrometry (GC-MS) platform optimized for this purpose.
(cont.) As an implementation proof-of-concept, we assayed metabolite levels across two different yeast strains and two different environmental conditions with the aim of metabolic pathway reconstruction. In doing so, we demonstrate that differential metabolite level data distinguish among sample types, such as those found in typical metabolic fingerprinting or footprinting techniques. More importantly, we demonstrate that this differential metabolite level data provides further insight into specific metabolic pathways. However, the data analysis of this GC-MS metabolomic profiling data relied upon reference libraries of metabolite mass spectra to structurally identify and track metabolites. In general, techniques to enumerate and track unidentified metabolites are non-systematic and require manual curation, thus requiring a novel method for computational mining of the spectral data for automated, exhaustive analysis. Accordingly, we developed a method and software implementation that can systematically detect components that are conserved across samples without the need for a reference library or manual curation. We validate this approach by correctly identifying the components in a known mixture and the discriminating components in a spiked mixture.
(cont.) Combining these robust capabilities to characterize metabolic state along with methods of measuring transcriptional states and protein interactions, we constructed a global network-based model of yeast amino acid biosynthesis containing 154 molecules, 37 rates, and 250 interactions to link genetic regulation and metabolic state. To interrogate this model, we created a battery of five genetic perturbations to the transcriptional regulators of amino acid biosynthesis and measured transcript levels, biomass 13C-labeling, and metabolite levels in batch culture. With this data, we designed a more detailed experiment to quantify 5764 mRNAs, 54 metabolites, and 83 experimental 13C-based reaction fluxes in continuous cultures of yeast under stress in the absence or presence of global regulator Gcn4p. While mRNA expression alone was insufficient to directly predict metabolic responses, this correlation improved through incorporating a network-based model of amino-acid biosynthesis (from r = 0.07 to 0.80 for mRNA-flux agreement). The model provides evidence of general biological principles: rewiring of metabolic flux by transcriptional regulation and metabolite-enzyme interaction density as a key biosynthetic control determinant.
by Joel Forrest Moxley.
Ph.D.
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Herbert, Jenny. "Genetic regulation of virulence in Streptococcus pneumoniae." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/4204/.
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S.pneumoniae is the leading cause of bacterial pneumonia and meningitis. Pneumonia alone has been estimated to kill more children under the age of five than that caused by AIDS, malaria and tuberculosis combined. The current vaccines which are used to prevent pneumococcal infection only protect against a small number of the 90+ serotypes currently identified. Current issues which may prevent the long term use of these vaccines is capsular switching, a phenomenon observed where some strains are able to escape the vaccine through switching their capsule genes. Further serotype replacement has been shown to occur since the introduction of the PCV7 vaccine, where serotypes not protected against by the vaccine have caused a higher incidence of invasive pneumococcal disease compared to the pre vaccine era. One strategy to avoid this is via the use of a multi-component protein based vaccine which is serotype independent. The pneumococcus is normally found as a harmless commensal yet can also cause invasive disease as stated above, the pneumococcus is also the leading cause of otitis media. The ability for the pathogen to occupy a number of different niches and evade host defences is attributed to its large cache of virulence factors, including numerous cell surface adhesins. The ability of the bacteria to regulate genes required for adaptation to a specified niche is vital for survival. In this study a number of signalling systems that are able to modulate gene expression (specifically virulence factors) to facilitate adaptation to varying environmental conditions are assessed to determine the genes they regulate. Further key environmental signals are evaluated to determine the effect they have on regulation of important cell surface adhesins. The main systems used to modulate global expression changes are two-component signal transduction systems (TCS). 13 TCS and one orphan response regulator are encoded in the pneumococcal genome. Little information is available with regards to the importance of each system, whether each system regulates its own separate collection of genes and the extent to which cross regulation may occur between these systems. This study used whole genome expression analysis data obtained through microarray analysis of single and double TCS mutants to assess the potential cross regulation of two chosen systems. A number of the systems have also been shown to regulate the same islet, which encodes a pilus. Measuring expression of the islet itself enabled the role of the systems shown to regulate the islet to be assessed for potential interactions between the systems and whether a hierarchy exists. The pneumococcus is highly genetically variable due to its ability to become naturally competent, taking up DNA from the environment and recombining it into its genomic DNA to aid genetic variation and survival. The new era of whole genome sequencing has begun to shed light on just how variable this pathogen is. Although a number of TCS have been shown to regulate pilus expression, with the use of whole genome sequencing of two closely related strains (one contains reduced pili expression levels) a number of other factors have also been identified which have been shown to alter pilus expression, this includes a serine/ threonine protein kinase, pyruvate oxidase and lactate oxidase. Further the pneumococcus has been shown to respond to exogenously added hydrogen peroxide which increases pilus expression levels. Levels of hydrogen peroxide may act as a key environmental cue to signal to the bacterium that they are present in the nasopharynx and require increased levels of cell surface adhesins.
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Sonnenberg, Sabine. "Tissue specific genetic regulation of Interleukin 6." Thesis, University of Southampton, 2009. https://eprints.soton.ac.uk/72590/.
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Interleukin 6 (IL6) is associated with arterial disease development, progression and surgical outcome. Raised levels of IL6 may play a causal role in disease development or may be the effect of pathology. An IL6 single nucleotide polymorphism (SNP) G- 174C has been identified and reported to associate with IL6 expression. However, conflicting results have emerged and both the relationship between IL6 and vascular disease and the precise effect of SNP G-174C in vivo in humans remains obscure. The aim of this study was to establish the effect of SNP G-174C in humans, in vivo in different tissues. Varicose vein surgery patients donated adipose tissue, skeletal muscle, vein and blood samples. Patients were genotyped for SNP G-174C. A new pre-mRNA assay was developed, using gel electrophoresis, restriction digest and fluorescence quantification, to measure the ratio of heterozygous allelic pre-mRNA transcription. IL6 mRNA expression in different tissues was also measured using relative real time PCR (RT-PCR) to assess effect of tissue type on expression profiles. mRNA expression within tissues was compared between G-174C genotypes, to further quantifying the association of SNP G-174C with transcript levels. The pre-mRNA assay showed higher expression for the C-allele, though not statistically significant. The pre-mRNA assay needed to detect low levels of intron retaining allelic pre-mRNA isoforms. Replicates and controls for residual genomic DNA were used to monitor assay precision. Adipose tissue gave the greatest precision in the pre-mRNA assay. In the RT PCR assay adipose tissue expressed significantly more IL6 mRNA than all other tissues examined. In vein and leukocytes subjects with the CC genotype expressed significantly higher levels of IL6 mRNA than subjects with GC or GG genotypes. There was a trend towards higher expression for the CC genotype in all tissue types. A significant though weak correlation between IL6 mRNA expression and age was demonstrated for vein and leukocytes. Adipose tissue may be an important source of IL6 compared to other tissues. This may be relevant for obesity associated diseases. Subjects with G-174C genotype CC showed a trend towards higher IL6 RNA expression. Further studies are necessary to clarify the effect of genotype on IL6 expression.
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葉志遠 and Chi-yuen Ip. "Characterization of the 5'flanking transcriptional regulation region of the chicken growth hormone gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31226115.
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Sule, Preeti. "Phenotypic and Genotypic Effects of FlhC Mediated Gene Regulation in Escherichia Coli O157:H7." Diss., North Dakota State University, 2011. https://hdl.handle.net/10365/29205.
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Escherichia coli (E.coli) 0157:H7, a pathogen belonging to the enterohemorrhagic group of E.coli, has long been a concern to human health. The pathogen causes a myriad of symptoms in humans, ranging from diarrhea and malaise to renal failure. Human infection with the spread of the pathogen is mainly attributed to consumption of contaminated food material such as meat. Decontamination of meat via sprays have to date been the most commonly practiced method to reduce contamination, which now has little relevance in the face of developing resistance by the pathogen. In the following study we investigated FlhC mediated gene regulation in E. coli 0157:H7 on the surface of meat, in an attempt to recognize FlhC regulated targets, which may ultimately serve as targets for the development of novel decontaminating sprays. Microarray experiments were conducted to compare gene expression levels between a parental E. coli 0157:H7 strain and its isogenic flhC mutant, both grown on meat. Putative FlhC targets were then grouped based on their function. Realtime PCR experiment was done to confirm the regulation. Additionally, experiments were done to investigate the phenotypic effects of the regulation. To test the effect of FlhC on biofilm formation, an ATP based assay was first developed in E.coli K-12, which has been detailed in the following dissertation. This assay was used to quantify biofilm biomass in E. coli 0157. Microarray experiments revealed 287 genes as being down regulated by FlhC. These genes belonged to functions relating to cell division, metabolism, biofilm formation and pathogenicity. Real-time PCR confirmed the regulation of 87% of the tested genes. An additional 13 genes were tested with real-time PCR. These belonged to the same functional groups, but were either not spotted on the microarray chips or had missing data points and were hence not included in the analysis. All 13 of these genes appeared to be regulated by FlhC. The phenotypic experiments performed elucidated that the FlhC mutants divided to 20 times higher cell densities, formed five times more biofilm biomass and were twice as pathogenic in a chicken embryo lethality assay, when compared to the parental strain. The following dissertation also reports the development of a combination assay for the quantification of biofilm that takes advantage of the previously mentioned ATP assay and the PhenotypeMicroarray TM (PM) system. The assay was developed using the parental E. coli strain AJW678 and later applied to its isogenic flhD mutant to elaborate on the differences in nutritional requirements between the two strains during biofilm formation. Metabolic modeling and statistical testing was also applied to the data obtained. This assay will be used in the future to study biofilm formation by the parental strain E. coli 0157:H7 strain and its isogenic FlhC
mutants on single carbon sources, hence identifying potential metabolites which differentially support biofilm formation in the parental and the mutant strain.
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Shek, Kim Fung. "Identification of cis-regulatory elements in mouse Mab21l2 gene by comparative genomics /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202010%20SHEK.
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Leung, Kei-chun Jane. "Purification of a transcriptional regulator of the dehalogenase IVa gene of Burkholderia species MBA4." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38734709.
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Champigny, Marc. "Expression of stem-loop binding protein during murine oogenesis and pre-implantation development." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21522.
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The goal of the work presented here was to investigate the hypothesis that cytoplasmic SLBP is required for translation of somatic H1 mRNA, and their translational repression is due to a lack of SLBP in the cytoplasm of oocytes, and early cleavage-stage embryos. To this end, the expression of SLBP in murine oocytes and pre-implantation embryos was characterized by RT-PCR, Western blotting, and immunocytochemical. techniques.mRNA encoding SLBP was detected throughout oogenesis and pre-implantation development, from small growing oocytes to the late blastocyst stage. SLBP protein was found in the nucleus and cytoplasm of growing and fully-gown prophase I-arrested oocytes. SLBP accumulated to extremely high levels during meiotic maturation in a process requiring translation. The protein remained abundant both in the nucleus and cytoplasm throughout the 1- and 2-cell stages. SLBP was depleted in 4-cell embryos in a process independent of DNA replication, and was not detected again until the late 8-cell stage. From the late 8-cell stage to the early blastocyst stage, SLBP was detected exclusively in the cytoplasm. Interestingly, in late blastocysts, SLBP was translocated to the nucleus. (Abstract shortened by UMI.)
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Chung, Yiu-kay Wilson, and 鍾堯基. "Identification of the regulatory element of dehalogenase IVa of Burkholderia cepacia MBA4." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29517291.
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Leung, Kei-chun Jane, and 梁奇珍. "Purification of a transcriptional regulator of the dehalogenase IVa gene of Burkholderia species MBA4." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38734709.
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Deng, Liyu, and 鄧麗瑜. "Exploration of the transcription factors that regulate the expression of the haloacid operon in Burkholderia caribensis MBA4." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208618.
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Bacterial dehalogenase is a key enzyme involved in bioremediation of halogenated organic compounds. A dehalogenase, Deh4a, was isolated from the Gram-negative bacterium Burkholderia caribensis MBA4, which can utilize haloacetic acids as carbon source. The haloacid operon in MBA4 was identified and characterized. It is composed of the structural genes forDeh4a and a transporter Deh4p. Transcription of this operon is negatively regulated, but the mechanism and the relevant regulator are still poorly understood. In this study, magnetic DNA affinity chromatography and Tn5transposon mutagenesis were employed to explore the regulatory factors that affected the expression of this haloacid operon.
A process that uses lysates from glycolate-grown cells, magnetic DNA affinity chromatography and LC-MS/MS has identified a TetR family transcriptional regulator, TetR8620, which binds to the promoter region of deh4a. Disruption of the TetR8620 gene in mutant Ins8620 abolished the formation of a slow migrating complex in electrophoretic mobility shift assay (EMSA) using lysates from glycolate-grown cells. Moreover, expressions of deh4a were enhanced in bothglycolate- and MCA- grown Ins8620. The addition of recombinant histidine-tagged TetR8620 to lysates of Ins8620 resumed the formation of a retardation complex, but different from that using purified His-tagged TetR8620.This suggested that TetR8620 is responsible for formation of retardation complexes, and an additional protein might be involved. To investigate other putative factors that interact with TetR8620, purified His-tagged TetR8620 was immobilized with Ni-NTA agarose and used for isolation of interacting proteins. Chemical cross-linking of the purified fraction with BS3established that TetR8620 interacts with a proteinof30 kDa. Separation of the cross-linked complex in SDS-PAGE gel also showed that a protein with similar MW was specifically pulled down. These results suggest that TetR8620 was interacting with a ~30 kDa protein. Protein identification using mass spectrometry assay proposed that this protein is probably a universal stress protein UspA encoding by peg.3485 or acetyl-glutamate kinase (EC 2.7.2.8) encoding by peg.714 in MBA4.
Tn5transposon mutagenesis was also employed to explore the factors that regulate the haloacid operon ofMBA4. A derivative of MBA4, MK06, which contains a kanamycin resistant gene (kan) with a deh4apromoter was constructed. Kanamycin resistancy of this derivative was MCA inducible. Transposon mutagenesis was conducted on this derivative, and Tn-containing mutants were isolated as tetracycline resistant colonies on pyruvate plates. These colonies were further selected on their resistance tokanamycin in pyruvate plates. Gene peg.6589 encoding a putative transcriptional regulator, DehR1, was disrupted by Tn insertion. While the production of dehalogenase was still MCA-inducible, this mutant has partially relieved the repression of the haloacid operon in media containing pyruvate. Moreover, constitutive production of DehR1 in MBA4 decreased the transcript levels of deh4ain medium containing pyruvate or MCA.
This study has identified two transcription factors, TetR8620 and DehR1, which regulate the expression of Deh4a negatively. TetR8620 is a DNA-binding protein that interacts with the deh4apromoter. Results from this study imply that the regulation of the haloacid operon in MBA4 is likely to be under the control of multiple factors.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
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Lorson, Christian. "An analysis of transcriptional regulation of the MVM capsid gene promoter." free to MU campus, to others for purchase, 1997. http://wwwlib.umi.com/cr/mo/fullcit?p9841319.
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Zak, Daniel Edward. "Structured modeling of mammalian transcription networks." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 374 p, 2005. http://proquest.umi.com/pqdweb?did=954050761&sid=7&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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林大偉 and Tai-wai Lam. "Structural organization, transcriptional regulation and chromosomal localization of the human secretin gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31224593.
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Holder, Kristina Kichler. "Dynamics of adaptive evolution in two experimental viral systems." Access restricted to users with UT Austin EID Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3037499.
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Hughes, Thomas. "The genetic regulation of Kranz anatomy in maize." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:86184e64-c7bb-43e9-9320-0ebbb2793ea8.
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The C4 photosynthetic pathway acts to concentrate CO2 around the enzyme Ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco), ensuring that it catalyses a carboxylation rather than oxygenation reaction, which in turn suppresses photorespiration. In nearly all cases C4 photosynthesis is underpinned by characteristic Kranz anatomy, with concentric wreaths of bundle sheath (BS) and mesophyll (M) cells surrounding closely spaced veins. The increased yields associated with the C4 pathway have lead to the suggestion that C3 crops such as rice should be engineered to undertake C4 photosynthesis, however, this goal is currently held back by a lack of understanding about how the development of Kranz anatomy is regulated. Recently, a number of candidate Kranz regulators have been identified in an RNA-seq study that compared leaf development in maize foliar (Kranz) and husk (non-Kranz) leaves. However, this study did not consider the impact of a recent whole genome duplication in the maize lineage on the gene expression patterns analysed. Therefore, in this thesis maize homeolog gene-pair divergence during early leaf development was assessed. This revealed that expression divergence of homeolog gene-pairs is a significant evolutionary phenomenon. Functional validation of a subset of Kranz candidates revealed that a Zmscr1-1; Zmscr1h-1 double mutant exhibited defects in Kranz patterning, including increased formation of extra BS cells and veins with no separating M cells. Furthermore, Zmnkd1; Zmnkd2 double mutants exhibited a subtle increase in extra BS cell formation. Taken together, this indicates that both ZmSCR1/ZmSCR1h and ZmNKD1/ZmNKD2 function redundantly during Kranz development. No evidence was obtained that two additional genes, ZmSHR2 and ZmRVN1, play a role in Kranz development, and expression of candidate Kranz regulators in rice did not alter leaf anatomy. Together, this work has confirmed roles for a number of genes in Kranz regulation, and has provided insight into the complex regulation underpinning Kranz development in maize.
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Tonning, Anna. "Genetic and molecular regulation of epithelial tube morphogenesis /." Göteborg : Institute of Biomedicine, Sahlgrenska Academy, Göteborg University, 2006. http://hdl.handle.net/2077/704.
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Hu, Yin. "Genetic polymorphism and regulation of cytochrome P450 2E1 /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3690-0.
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Iatan, Iulia. "Novel genetic and molecular regulation of HDL metabolism." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121170.
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Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. Low levels of high-density lipoprotein cholesterol (HDL-C) constitute a major independent risk factor for CAD, influenced by a combination of genetic and environmental factors. In this thesis, we aimed to advance our understanding of the genetic regulation of HDL-C, through the identification and characterization of novel candidate genes, and to delineate the molecular mechanisms underlying HDL biogenesis, in the hopes of better elucidating the complexities of HDL metabolism. First, we examined whether variation at the PCSK5 gene locus influences HDL-C levels. Through familial segregation analyses and two-stage genetic association studies in unrelated subjects of French Canadian descent and low HDL-C Finnish families (ntotal=883), we reported a region-wide significance of PCSK5 SNPs with HDL-C, suggesting that genetic variability at the PCSK5 locus regulates HDL-C levels, possibly through the inactivation of endothelial lipase. Second, to search for rare-low frequency variants responsible for low HDL-C, we used whole exome sequencing in a multigenerational French Canadian family (n=75) with HDL-C<5th age-sex specific percentile. Through this approach, we identified a complex combination of two non-synonymous variants, in the ATP-binding cassette transporter (ABCA1) and the lipoprotein lipase genes, predicted to be damaging and causing low HDL-C. These results emphasize the need for exome sequencing of complex lipid traits in unexplained familial cases. Third, we sought to characterize a novel genetic determinant involved in HDL-C regulation. Recent studies from our group identified the WW domain-containing oxidoreductase (WWOX) gene locus to be associated with low serum HDL-C levels in 9,798 subjects. In this study, we examined the role of WWOX in lipoprotein and HDL metabolism using a combination of in vivo functional studies, by means of total Wwox knock-out and Wwox liver-specific mouse models, gene microarray and next generation resequencing analyses in HDL-deficient French Canadian families. We demonstrated that the effects of WWOX on lipoprotein metabolism involve multiple mechanisms, including cholesterol homeostasis, apoA-I and ABCA1-mediated pathways and fatty acid/triglyceride metabolism. Fourth, with novel insight into genetic regulations of HDL metabolism, we focused on elucidating the mechanistic basis of nascent HDL formation. Specifically, we investigated the lipidation of ApoA-I and its interaction with an ABCA1/phosphatidylcholine(PC)-rich microdomain, the high-capacity binding site (HCBS). Using sucrose gradient fractionation, we also demonstrated that the ABCA1/ HCBS partitions to nonraft domains, thus playing a pivotal role in the selective desorption of PC molecules by apoA-I, creating an optimal environment for nascent HDL formation and cholesterol release.In summary, this work has collectively advanced our understanding of the molecular and genetic basis of HDL metabolism. It has brought to light novel genes governing plasma HDL-C levels in humans, highlighting the need to use multiple integrative genetic approaches to identify causal common and rare variants conferring susceptibility to low HDL-C. These findings have also helped elucidate the mechanistic basis of the nascent HDL genesis pathway. Together, this thesis has combined genetic and biochemical strategies to provide a more comprehensive understanding of the complexities of the HDL metabolism and cellular cholesterol transport, which may lead to the characterization of novel therapeutic targets for CAD.La maladie coronarienne athérosclérotique (MCAS) est la principale cause de mortalité et de morbidité à l'échelle mondiale. Un niveau bas des lipoprotéines de cholestérol de haute densité (HDL-C) représente un facteur de risque majeur pour la MCAS et est influencé par une combinaison des facteurs génétiques et environnementaux. Dans cette thèse, nous avons abordé la régulation génétique des HDL-C grâce à l'identification et la caractérisation de nouveaux gènes candidats, et de mécanismes moléculaires liés à la biogenèse des HDL, dans l'espoir de mieux élucider la complexité du métabolisme des HDL.En premier, nous avons examiné si la variation au niveau du locus du gène proprotéine convertase PCSK5 peut affecter les niveaux de HDL-C. Grâce aux analyses de ségrégation familiale et aux études d'association génétique dans une population canadienne-française et chez des familles finlandaises (nTotal=883) avec un niveau de HDL-C bas, nous avons constaté une large corrélation régionale entre les variations polymorphiques (SNPs) de PCSK5 et HDL-C. Ceci suggère que la variabilité génétique au niveau du locus PCSK5 réglemente le HDL-C, éventuellement par le biais de l'inactivation de la lipase endothéliale, une enzyme clé dans la modulation des niveaux plasmatiques de HDL-C. Deuxièmement, pour rechercher des variants de fréquence rare qui sont responsables d'un bas niveau de HDL-C, nous avons utilisé la technique du séquençage de l'exome dans une famille multi-générationnelle canadienne-française (n=75) avec un HDL-C<5e percentile spécifique (âge-sexe). Grâce à cette approche, nous avons identifié une combinaison complexe de deux variants non-synonymes dans le transporteur ABCA1 et dans le gène de la lipoprotéine lipase provoquant un taux faible de HDL-C. Ces résultats soulignent la nécessité du séquençage de l'exome des traits lipidiques complexes dans les cas familiaux inexpliqués. Troisièmement, nous avons caractérisé un nouveau gène impliqué dans la régulation du HDL-C. Nous avons examiné le rôle de WWOX dans le métabolisme du HDL en utilisant des études fonctionnelles in vivo avec des souris Wwox total knock-out (KO) et des souris Wwox KO spécifiques au foie, une technologie des puces à ADN et du reséquençage dans des familles canadiennes-françaises déficientes en HDL. Nous avons démontré que l'effet de WWOX sur le métabolisme des lipoprotéines implique plusieurs mécanismes, y compris l'homéostasie du cholestérol, les voies de régulation à travers l'ApoA-I et l'ABCA1 et le métabolisme d'acides gras/triglycérides. Quatrièmement, nous voulions élucider le mécanisme de formation du HDL naissant. Plus précisément, nous avons étudié la lipidation de l'ApoA-I et son interaction avec des sites constitués de microdomaines ABCA1/phosphatidylcholine (PtdC) que nous avons appelés « site de liaison de grande capacité (HCBS) ». En utilisant un gradient de densité de sucrose, nous avons observé que l'ABCA1 et le HCBS sont localisés dans des domaines membranaires solubles aux détergents et que l'ApoA-I désorbe sélectivement la PtdC de ces domaines ainsi créant un environnement optimal pour la formation des molécules naissantes de HDL et la libération de cholestérol.Collectivement, ce travail a élargi notre compréhension des sciences moléculaires et génétiques du métabolisme du HDL. Il a mis en lumière de nouveaux gènes impliqués dans la régulation des niveaux de HDL-C, soulignant la nécessité d'utiliser plusieurs approches intégratives génétiques pour identifier les causes des variants communs et rares conférant une susceptibilité à un faible taux de HDL-C. Ces résultats ont également contribué à élucider le mécanisme de biogenèse du HDL naissant. Ainsi, cette thèse a combiné des stratégies génétiques et biochimiques pour fournir une meilleure compréhension de la complexité du métabolisme des HDL et du transport du cholestérol cellulaire, qui pourrait ainsi conduire à l'élaboration des nouvelles cibles thérapeutiques pour la MCAS.
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Howard, Sasha. "Investigation of the genetic regulation of delayed puberty." Thesis, Queen Mary, University of London, 2017. http://qmro.qmul.ac.uk/xmlui/handle/123456789/28165.
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The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern and is highly heritable; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern and is highly heritable; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Our large, accurately phenotyped cohort of patients with familial self-limited DP is a unique resource with a relatively homogeneous genetic composition. I have utilised this cohort to investigate the genetic variants segregating with the DP trait in these pedigrees. Whole exome sequencing in eighteen probands and their relatives, and subsequent targeted sequencing in an extended subgroup of the cohort, has revealed potential novel genetic regulators of pubertal timing. In ten unrelated probands, I identified rare mutations in IGSF10, a gene that is strongly expressed in the nasal mesenchyme during embryonic migration of gonadotropin-releasing hormone (GnRH) neurons. IGSF10 knockdown both in vitro and in a transgenic zebrafish model resulted in perturbed GnRH neuronal migration. Loss-of-function mutations in IGSF10 were also identified in five patients with absent puberty due to hypogonadotropic hypogonadism (HH). Additionally, I have identified and investigated one rare, pathogenic mutation in HS6ST1 - a gene known to cause HH - in one family with DP, and two rare variants in FTO - a gene implicated in the timing of menarche in the general population - in 3 families. Further potentially pathogenic variants have emerged from investigating candidate genes identified from microarray studies (LGR4, SEMA6A and NEGR1) and from related clinical phenotypes (IGSF1). Our large, accurately phenotyped cohort of patients with familial self-limited DP is a unique resource with a relatively homogeneous genetic composition. I have utilised this cohort to investigate the genetic variants segregating with the DP trait in these pedigrees. Whole exome sequencing in eighteen probands and their relatives, and subsequent targeted sequencing in an extended subgroup of the cohort, has revealed potential novel genetic regulators of pubertal timing. In ten unrelated probands, I identified rare mutations in IGSF10, a gene that is strongly expressed in the nasal mesenchyme during embryonic migration of gonadotropin-releasing hormone (GnRH) neurons. IGSF10 knockdown both in vitro and in a transgenic zebrafish model resulted in perturbed GnRH neuronal migration. Loss-of-function mutations in IGSF10 were also identified in five patients with absent puberty due to hypogonadotropic hypogonadism (HH). Additionally, I have identified and investigated one rare, pathogenic mutation in HS6ST1 - a gene known to cause HH - in one family with DP, and two rare variants in FTO - a gene implicated in the timing of menarche in the general population - in 3 families. Further potentially pathogenic variants have emerged from investigating candidate genes identified from microarray studies (LGR4, SEMA6A and NEGR1) and from related clinical phenotypes (IGSF1).
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Broadbent, Ian David. "Genetic regulation of cellular morphogenesis in Candida albicans." Thesis, University of Aberdeen, 1997. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU528921.
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This work attempts to gain information about the molecular basis of the yeast-to-hypha morphological transition in Candida albicans by investigating the roles of two genes that have been postulated to exert an influence over this process. A C. albicans cDNA had been previously isolated during a screen for cDNAs that encode immunogenic proteins specific to the hyphal form of C. albicans. Sequencing of cDNA10 in this study and database searches indicated that cDNA10 shows a high level of sequence identity to two closely related Saccharomyces cerevisiae ribosomal proteins, Rp10Ap and Rp10Bp. This C. albicans gene was therefore renamed RP10. However, subsequent Northern analysis by Rolf Swoboda showed that the RP10 did not respond to hyphal development per se, but was tightly regulated during growth. It was concluded that RP10 is unlikely to be a regulator of hyphal development in C. albicans. The role of the HST7 MAP kinase kinase was also investigated. An HST7overexpression plasmid was constructed using a novel C. albicans expression vector created in this study, and phenotypic effects of HST7 overexpression in C. albicans and S. cerevisiae were determined. Overexpression of HST7 promoted pseudohyphal growth in a S. cerevisiae diploid strain under conditions of nitrogen starvation, and suppressed the pseudohyphal defects in S. cerevisiae ste 7/ste7 and ste11/ste11 strains. However, HST7 overexpression did not promote constitutive pseudohyphal growth in S. cerevisiae. Overexpression of HST7 suppressed the hyphal defect in a C. albicans hst7/hst7 null mutant, although HST7 overexpressed did not promote constitutive hyphal growth in C. albicans. HST7 is there suggested to be a member of a pathway that is necessary for hyphal growth in C. albicans under some conditions.
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Baird, Nathan Alder. "Hypoxic gene regulation and high-throughput genetic mapping. /." Connect to title online (ProQuest), 2008. http://proquest.umi.com/pqdweb?did=1525703731&sid=1&Fmt=2&clientId=11238&RQT=309&VName=PQD.
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Thesis (Ph. D.)--University of Oregon, 2008.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 45-52). Also available online in ProQuest, free to University of Oregon users.
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Bayer, Travis Scott Arnold Frances Hamilton Smolke Christina D. "Synthetic control and genetic regulation of ecological strategy /." Diss., Pasadena, Calif. : California Institute of Technology, 2009. http://resolver.caltech.edu/CaltechETD:etd-10162008-131654.
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