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1

Willer, Cristen. "Genetic and environmental susceptibility to multiple sclerosis." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275379.

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2

Lincoln, Matthew R. "Candidate gene studies and fine-mapping of the mjor histocompatibilty complex association in multiple sclerosis." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427634.

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3

Berggren, Bremdal Karin. "Evolution of MHC Genes and MHC Gene Expression." Doctoral thesis, Uppsala universitet, Evolutionsbiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011.

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Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times. MHC genes encode antigen-presenting molecules in the adaptive immune system, which protects the host from infectious diseases. However, MHC molecules may also present self-peptides and for most autoimmune diseases there is a genetic factor associated with the MHC. MHC genes have been used to learn about the interplay of selection and historical population events. In domestic dogs and their progenitor, the wolf, I explored factors associated with domestication and breed formation and their influence not only on MHC coding regions but also on the haplotypic structure of the class II region. Polymorphism and strong selection was demonstrated in the proximal promoters of MHC genes in dogs and wolves. Hence, genetic variation associated with MHC gene expression may have at least equal importance for a well functioning immune system. Associations between promoter sequences and particular coding alleles suggested allele-specific expression patterns. SNP haplotypes of the MHC class II region revealed ancestral as well as convergent haplotypes, in which combinations of alleles are kept by selection. Interestingly, weaker allelic associations were found between different genes and between coding regions and promoters in dogs compared to wolves. Potentially, this could cause insufficient defense against infections and predispose dogs to autoimmune diseases. For example, I identified a site in the promoter region that showed a consistent difference between haplotypes conferring susceptibility and protection to diabetes in dogs, which should be investigated further. Furthermore, I investigated how selection and demographic changes associated with glacial and inter-glacial periods have affected MHC variation in European hedgehogs and extended the prevailing knowledge concerning their population history.
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4

Hirni, Helen. "The Major histocompatibility complex in horses /." [S.l : s.n.], 1988. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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5

Laguna, Goya Rocío. "Major histocompatibility complex and stem cells." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608773.

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6

Brown, Jason John. "Polymorphisms of the equine Major Histocompatibility Complex." Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406666.

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7

Paterson, Stephen. "Major histocompatibility complex variation in Soay sheep." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627271.

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8

Kemp, Stephen John. "The major histocompatibility complex of African cattle." Thesis, University of Edinburgh, 1985. http://hdl.handle.net/1842/15146.

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9

Kendall, Elaine. "Molecular characterisation of the human major histocompatibility complex." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333402.

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10

Takousis, Petrus. "DNA replication in the human major histocompatibility complex." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445119/.

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DNA replication is a vital component of the eukaryotic cell cycle. During the course of S-phase, numerous origins of replication become activated along each chromosome. Several adjacent origins fire synchronously to replicate large sections of a chromosome at specific times. Early studies identified a relationship between cytogenetic bands and replication timing: GC-rich R-bands replicate early while AT-rich and gene poor G-bands replicate late, apparently regardless of differentiation and developmental status. Subsequent studies revealed that other factors such as transcriptional status also influence the replication programme. The aim of this thesis is to examine the organisation of DNA replication in the human Major Histocompatibility Complex (MHC) on chromosome 6, and understand how it relates to gene expression and inherent genomic properties. A previous investigation from the Human Cytogenetics Laboratory using fluorescence in situ hybridisation (FISH) suggested that replication timing of the MHC is organised into distinct zones, with the MHC class II region, an AT-rich isochore, replicating later than neighbouring regions. Using a biochemical approach, the entire MHC was found to replicate within the first half of S-phase in cell lines derived from different tissues. Subsequent analysis of a B-lymphoblastoid cell line using a high resolution tiling path array for the MHC confirmed that a large proportion of the MHC class II replicates later than its neighbours. The data suggested the existence within the MHC of replication origins that fire at distinct times in S-phase. An investigation of replication initiation in the MHC revealed the presence of several potential initiation sites, which were further analysed by quantitative PCR. The gene-rich MHC class III was found to have a relatively large number of replication initiation sites. Overall, these results suggest that either specific origins of replication or zones of initiation can fulfill the replication requirements of a region.
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11

Dunham, Ian. "Molecular mapping of the human major histocompatibility complex." Thesis, University of Oxford, 1988. http://ora.ox.ac.uk/objects/uuid:61559181-d77f-479e-8bfe-2e324d8806bd.

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2. The long range DNA organisation of the class II and class III regions in eight HLA homozygous cell lines has been analysed using PFGE. Comparison of the size of the BssHII restriction fragment observed for these cell lines and five individuals possessing one to three C4 genes, shows that the organisation of the C4 genes on each chromosome can be deduced from a single PFGE experiment. Outside of the C4 and 21-OHase loci the class III region shows a highly invariant structure, with no detectable differences in the amount of DNA present. Moreover the class III region is rich in CpG-islands, one of which has been characterised, and contains at least thirteen new genes. However, in the class II region, two differences between common haplotypes have been found. The DRw52-related haplotypes have the same DNA organisation. DR2 haplotypes possess 20-30 kb more DNA in the DRB region. DRw53 haplotypes have 100-130 kb more DNA than DRw52-related haplotypes in the region containing the DRB and DQA genes.
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12

Daniels, Wayne W. "Association of the Major Histocompatibility Complex with Autism." DigitalCommons@USU, 1996. https://digitalcommons.usu.edu/etd/4658.

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The pathogenesis of autism has proven difficult to characterize. However, in many recent studies, it is suggested that the onset of this disorder is the result of multiple etiological factors, which include genetic, immunologic, and viral elements. Possible immunological influences found in subpopulations of patients with autism include decreased lymphocyte responsiveness, reduced natural killer cell activity, abnormal response to rubella vaccine, abnormal immune response to brain tissue, and decreased plasma levels of the fourth component of complement(C4). These aberrations and others imply a possible autoimmune mechanism in some cases for the development of autism. C4 deficiencies have been found in subjects with established autoimmune disorders, such as systemic lupus erythematosus and chronic active hepatitis, in recent investigations. There is also evidence that the major histocompatibility genes play an intimate role in autoimmune processes. Therefore, in knowing that the C4 genes are closely linked to the major histocompatibility genes, this study determined and analyzed the human leukocyte antigen profile of autistic patients, their siblings, and parents. In this study, it was found that the C4B complement null allele occurred in autistic patients at nearly twice the frequency compared to normals. However, the C4A complement null allele frequency was not found to be significantly altered. Several extended haplotypes were represented within the patients studied. However, the extended haplotype B44- SC30-DR4 was the only one found at a significantly increased frequency. Further investigations are needed to better understand the significance of these findings.
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13

Ottaviani, D. "The genomic anchors of the human major histocompatibility complex." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/16303/.

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Eukaryotic chromatin is organised into a hierarchy of topologically constrained loop structures. Matrix Attachment Regions (MARs) are genomic sequences that mediate the anchoring of chromatin to the insoluble proteinaceous fraction of the nucleus known as the nuclear matrix. Since only a few MARs have been characterised so far, their role in genomic structure and function is not well understood. The aim of this thesis is to use the human Major Histocompatibility Complex (MHC) as model region to provide novel insights into the relationship between chromatin folding mediated by MARs and gene expression. This large locus contains critical genes for immunity and is associated with more diseases than any other genomic region. Classical MHC genes are expressed in a cell type specific pattern, and can be induced by cytokines such as IFN-γ. MARs were identified across the entire MHC in uninduced fibroblasts, IFN-γ induced fibroblasts and B lymphoblastoid cells. Expression array analysis showed that these cell types exhibit different MHC expression profiles. MARs were first isolated treating nuclei with hypertonic buffers followed by nuclease digestion and then mapped by hybridizing them onto a novel tiling path array for the MHC. The suitability of this array platform to study DNA-protein interactions was verified using hybridisations of CIITA-enriched DNA and DNA enriched in H3-K9/K14 acetylation. The findings reveal that MARs are unevenly distributed across the MHC, and that they can be classified into three classes: constitutive, cell type specific and transcriptiondependent. These sequences are mainly positioned in intergenic regions and in close proximity to the MHC class boundaries, subdividing the locus into physical domains. By comparing the position of MARs in uninduced fibroblasts, IFN-γ induced fibroblasts and B lymphoblastoid cells, transcriptional activation of the MHC was found to be associated with a reconfiguration of chromatin architecture resulting from the formation of additional genomic anchors. These results suggest that the dynamic tethering of chromatin is linked to transcriptional regulation.
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14

Godinez, Ricardo. "Comparative Genomics of the Major Histocompatibility Complex in Amniotes." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10685.

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The major histocompatibility complex region (MHC) is a multi gene family present in all jawed vertebrates, with a fundamental role in vertebrate immunity. More than two decades of studies have resulted in the characterization of over a dozen MHC regions, and models of evolution explaining that the MHC has gradually increased in size and gene content since its origins without addressing their genomic context or the environmental selective forces. Furthermore, a compelling reconstruction of the evolutionary history of the MHC has been hampered due to phylogenetic gaps and the absence of comparative phylogenetic methods applied to comparative genomics. Here I reconstruct 320 MY of MHC evolution using 42 amniote genomes using improved gene annotations, genomic alignments and phylogenetic algorithms to reconstruct the evolution of the MHC at three levels of phylogenetic resolution. The first one describes 25 MY of evolution of the primate MHC using eight Human and four non-Human primate MHC haplotypes. Results suggests that highly dense gene segments have a strikingly conserved gene organization, and six conserved and highly rearranging segments overlap genes that are most commonly associated to disease. Phylogenomic analysis implies that the MHC has remained stable in gene content and size, with significantly increased duplication rates in the primate ancestors. The second one describes 280 MY of MHC evolution through the first characterization of reptilian MHC region, which combines mammalian, reptilian, Bird and amphibian characteristics, which favors the hypothesis of the existence of a primordial MHC in which natural killer receptors, CD1 and lectin genes co-exist. The Anolis MHC expands our understanding of the origins of the exceptionally small Bird MHC regions and provides further information about the organization and size of the ancestral amniote MHC. The third one compares 42 amniote MHC regions and map gene duplications and losses to further evaluate the mode and tempo of the evolution of the region. Comparative phylogenetic methods imply that the genomic and environmental factors affect the diversification of MHC during 320 My of evolution.
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15

Plant, Katharine. "Allele specific gene expression in the major histocompatibility complex." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:f565a41c-4699-4416-b1be-150b6a87dd0f.

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The Major Histocompatibility Complex (MHC) is a highly polymorphic region of the genome located on chromosome 6p21 in which genetic diversity has been associated with susceptibility to many autoimmune, infectious and other common diseases. Despite strong associations between disease and variation in the MHC that have been identified initially from serological testing and more recently by genome-wide association studies, functional insights into how specific variants may be altering disease susceptibility remain poorly understood in most cases. It is predicted that gene expression will play a significant role in the modulation of disease susceptibility and so further understanding of allele specific gene expression in the MHC will be necessary to help define the function of disease associated variants in this region. This thesis aimed to define allele specific gene expression in the MHC by characterising specific candidate genes together locus-wide approaches in order to try and resolve functional variants. Gene expression was analysed in both lymphoblastoid cell lines (LCLs) and primary human peripheral blood mononuclear cells (PBMCs). Data is presented validating a novel haplotype-specific MHC microarray and fine mapping putative local, likely cis-acting, regulatory variants. This was done by expression quantitative trait mapping for two cohorts of healthy volunteers. A transcription factor ZFP57, encoded in the MHC, was found to show significant differential allelic expression relating to specific single nucleotide polymorphisms (SNPs) and possession of HLA-type. This provided new insights into reported disease associations, notably HIV-1 infection and cancer. The function of ZFP57 was further investigated in terms of genome-wide DNA binding sites by ChIP-seq together with its binding co-factor KAP1. Allele-specific gene expression was also demonstrated for several classical HLA genes including the HLA-C and HLA-DQ genes, fine mapping specific putative regulatory variants. This provided new insights into disease association, notably variants of HLA-DQB1 and susceptibility to leprosy. The applicability and sensitivity of the technique of RNA sequencing (mRNA-seq) for allele-specific quantification of gene expression was investigated for different allelic ratios of RNA from LCLs homozygous for sequence across the MHC. Significant challenges were identified in successful application of this technique to MHC genes while high levels of accuracy were observed dependent on read depth in non-MHC genes. This thesis provides new insights into the extent and nature of allele-specific gene expression in the MHC, experimental approaches that can be used and insights gained into disease susceptibility for this important genomic region.
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16

Maxey, Gail D. "Identification of major histocompatibility complex haplotypes in goldfish, Carassius auratus." Thesis, This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-08042009-040408/.

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17

Ward, Joshua Mark. "Major histocompatibility complex-mediated behaviour : a case for visual cues." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608239.

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18

Glithero, Ann. "Presentation of glycopeptides by major histocompatibility complex (MHC) class I." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267901.

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19

Bos, David H. "Statistical genetics and molecular evolution of major histocompatibility complex genes." Thesis, University of Canterbury. Biological Sciences, 2005. http://hdl.handle.net/10092/6773.

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MHC region genes have been the subject of molecular evolutionary studies both from single species and from a variety of taxa. The African clawed frog, Xenopus laevis, provides a good model for the study of immune genes such as the MHC class Ia because of the genomic architecture of the MHC region. Herein, I investigate 1) the molecular evolution of the MHC class Ia gene at the population level in X laevis, and 2) the evolution of proteasome subunits psmb5 and lmp7 following duplication from their common ancestral locus using a phylogenetic sampling of mainly vertebrate taxa. Modelbased maximum likelihood statistical procedures are used in an effort to overcome typical problems associated with complex patterns of molecular evolution at these loci. In this thesis I present several new findings, and Chapters I and II focus on phylogenetic investigation of proteasome subunits. Results indicate that several evolutionary mechanisms operate on lmp7 that makes phylogenetic reconstruction of this locus difficult. I show that analysis of this gene is sensitive to the particular assumptions of various models of nucleotide evolution commonly used for phylogenetics. I also investigate whether or not natural selection operated differentially on duplicates of the proto-lmp7 gene locus. I provide evidence that positive Darwinian evolution contributed to the functional divergence of gene family members derived from this locus-making this one of the few examples of positive natural selection operating on a protein with housekeeping functions. Several new and major findings are also presented for the X. laevis class la MHC gene in Chapters III, IV and V. For the first time I provide robust estimates of substitution rates that show the operation of natural selection on peptide binding region (PBR) amino acids of the class la gene. I also show for the first time that intralocus recombinations are a major source of variation in the class la gene in X. laevis. Patterns of polymorphism at the class la locus are investigated in greater detail, and provide evidence for a molecular basis driving the coevolution of functionally linked genes. Combining data from other species, my results also demonstrate that the mode of MHC class la evolution is different than the classical paradigm detailed in mammals. Finally, my research is the first to demonstrate that non-linkage of the class I and class II genes in a single genomic region is not always necessary for this mode of class la evolution, as previously expected.
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20

Smith, Kyrlie Brooke. "Expression of major histocompatibility complex class I genes in cattle." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312574.

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21

Hypes, Kaleb Marie. "Docosahexaenoic acid modulates Class I major histocompatibility complex protein function." Huntington, WV : [Marshall University Libraries], 2004. http://www.marshall.edu/etd/descript.asp?ref=433.

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22

Keating, Paula. "Major histocompatibility complex class II expression on ovine T cells." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/30336.

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In this study the expression of MHC class II molecules on T cells from various immunological compartments of the sheep was examined. Monoclonal antibodies (mAbs) were characterized which react specifically with the homologues of human DRα and DQα molecules. The expression of these antigens was established on B cells and T cell subsets derived from peripheral blood, efferent lymph and afferent lymph. B cells from each of the lymphocyte sources expressed both DRα and DQα antigens. Variable expression on T cells was found. Each of the T cell subsets expressed both DR and DQ molecules at much higher levels in afferent lymph. DR expression on peripheral blood lymphocytes and efferent lymphocytes was higher than DQ on each of the T cell subsets. Afferent lymphocytes represent memory type cells and class II DR expression on these T cells may mark activation status. Expression of the class II subtypes was also examined on in vivo activated T cells and correlated with expression of activation markers. Increased expression of class II molecules was coincident with the increased expression of activation markers in each of the T cell subsets with the exception of γδ cells. The lack of correlation on γδ T cells may be a reflection on the type of antigen used. Levels of DQ expression on CD4 positive cells after activation showed a more dramatic increase than levels of DR expression. Cytokine profiles of concanavalin A (Con A) activated T cells (DR positive) were examined and compared with that of DR negative T cells. The data reveal that IL-6 mRNA production correlated with DR expression. IL-6 was induced after activation of the total T cell population and was not induced in the DR negative T cells. No detectable differences in IL-4, Il-10 and γIFN mRNA profiles were observed between the total T cell population and the DR negative T cells.
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23

Wright, Harry. "Genes of the ovine major histocompatibility complex class II region." Thesis, University of Edinburgh, 1996. http://hdl.handle.net/1842/30049.

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As part of a study investigating fundamental cellular immunology in the sheep, this thesis describes the characterisation and expression of the genes of the sheep MHC class II region. Cosmid libraries prepared from DNA from three unrelated sheep were screened with probes from the DP, DQ and DR sub-regions of the human and mouse MHC class II regions. Cosmids were used because they facilitate the cloning of relatively large genomic inserts. Restriction maps of the cosmids have been produced showing that some of the clones overlapped. The MHC A and B genes within the clones have been sequenced and assigned to a specific sub-type. Functional genes have been identified by the reaction of their products with anti-sheep class II monoclonal antibodies following DNA-mediated transfection into the mouse L cell, a fibroblast cell line which does not express endogenous mouse class II genes. Transcription of some of the genes has been demonstrated by Northern blots and reverse transcription polymerase chain reaction. A restriction map of the sheep class II DQ sub-region has been constructed and shown to contain two distinct DQA loci with associated DQB genes. The DQ1 A/B gene pair was expressed in the mouse L cell. The sheep class II DQ1 product at the cell surface reacted with a sub-set of the available anti-sheep class II monoclonal antibodies. The DQ2 genes were transcribed and some evidence for their cell surface expression was obtained, although this was not formally proved.
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24

Go, Yasuhiro. "Characterization and evolution of major histocompatibility complex genes in prosimians." 京都大学 (Kyoto University), 2003. http://hdl.handle.net/2433/149146.

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25

Lo, Yun-hua. "A preliminary survey of MHC class I sequences in mandrills." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648208.

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26

Parker, Kay Elizabeth. "Genetic and immunological studies on class I MHC antigens of the rat." Thesis, Open University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278511.

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27

Mawas, Fatme Omar. "Expession of MHC molecules on rat cardiac cells : its effect on their immunogenicity in vitro." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283719.

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28

Rogers, Sarah Louise. "Characterisation of C-type lectin-like receptor genes in the chicken MHC." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271871.

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29

Lim, Elaine Hsuen. "Study of Fugu orthologues of mammalian MHC class III genes." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266288.

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30

Ramsay, Joshua David. "Development of a DNA microarray for detection of expressed equine classical MHC class I alleles in a defined population." Pullman, Wash. : Washington State University, 2009. http://www.dissertations.wsu.edu/Thesis/Fall2009/j_ramsay_112309.pdf.

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Thesis (M.S. in veterinary science)--Washington State University, December 2009.
Title from PDF title page (viewed on Jan. 14, 2010). "College of Veterinary Medicine." Includes bibliographical references (p. 12-13).
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31

葉德俊 and Tak-chun Timothy Yip. "Characterization of a monoclonal antibody reactive against major histocompatibility complex class II antigens." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1992. http://hub.hku.hk/bib/B3123334X.

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32

Yip, Tak-chun Timothy. "Characterization of a monoclonal antibody reactive against major histocompatibility complex class II antigens /." [Hong Kong] : University of Hong Kong, 1992. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13478771.

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33

Matuszek, Gregory H. "Characteristics of the class I major histocompatibility complex of the Macaca fascicularis /." Link to online version, 2005. https://ritdml.rit.edu/dspace/handle/1850/1120.

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34

Feichtlbauer-Huber, Petra. "Einfluss des major histocompatibility complex (MHC) auf die Nematodenanfälligkeit beim Schaf." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964457458.

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35

Qin, Jinyi. "Characterisation of the central region of the sheep major histocompatibility complex." Curtin University of Technology, School of Biomedical Sciences, 2008. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=118317.

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The major histocompatibility complex (MHC) is a chromosomal region encoding molecules controlling adaptive immune response in vertebrates. In farm animals, many associations between MHC loci and productivity traits including disease susceptibility have been described. However, current knowledge about the structure and function of the MHC in domestic animals, especially sheep, is very limited. Characterization of the sheep MHC may potentially facilitate breeding for enhanced disease-resistant animals through use of marker assisted selection. The main aim of this project has been to provide insights into the organization of the genomic content of the central region of the sheep MHC. The work described herein has utilized subcloning of a sheep BAC genomic library in conjunction with DNA sequencing to generate a map of the central region of the sheep MHC covering ≈700 kbp. Within this map the relative order and identity of twenty five recognized loci were established. For some loci the intergenic distances were also determined. The final map is the most accurate map of this region reported to date and shows a high degree of similarity to the analogous region of the human MHC. This work has been published and a copy of the paper is included in Appendix 1. During the course of this work detailed genomic sequences were obtained for several sheep central region loci. Complete nucleotide sequences were generated for the complement factor B locus (CFB) and the TNFα locus and a comparative analysis of these sequences confirmed their homology with other vertebrate orthologues. Extensive partial sequences for complement components C2 and C4 were also obtained and reported to GenBank.
In addition, a previously identified short tandem repeat locus designated BfMs believed to be in the CFB locus was mapped to an intron within the adjacent SKI2VL locus. Single nucleotide polymorphisms (SNPs) were identified by analysing homologous sequences from a minimum of five individual sheep. In total 33 SNPs were discovered distributed over eleven distinct loci. Allele frequencies for SNPs from ten of these loci were determined and reported for a panel of 71 sheep comprising 58 unrelated sheep from the Rylington Merino flock plus a further 13 unrelated parental animals from a three generation half sibling sheep pedigree. The availability of an independently confirmed pedigree constructed from a three generation half sibling sheep family permitted the identification by deduction of central region MHC haplotypes based on a panel of SNPs derived from 10 loci. This is the first reporting of haplotypes covering this region of the sheep MHC. Analysis of SNP panel genotypes in the cohort of 71 unrelated sheep using the expectation maximization algorithm permitted the prediction of a group of approximately 20 haplotypes, which accounted for more than 90% of the expected haplotype distribution. Four of these predicted haplotypes were also present in the known haplotype cohort deduced from the sheep pedigree. Analysis of pairwise linkage disequilibrium between SNP loci in the cohort of 71 unrelated sheep showed a centre-most region displaying relatively high levels of linkage disequilibrium which was bounded by two regions displaying more variable linkage disequilibrium.
It is hypothesised that this mid region of the central region of the sheep MHC may be a block like structure characterized by low recombination similar to those that have been widely described in the human and mouse genomes. The discoveries reported in this thesis provide a more accurate and detailed description of the central region of the sheep MHC together with a panel of SNPs, which reflect the diversity of this important genomic region which is known to be associated with immune responsiveness. The description, for the first time, of central region haplotypes provides a practical means of seeking candidate loci associated with disease resistance and productivity traits. The application of molecular techniques will enhance the rate at which the genomic composition of this region is elucidated and the work described in this thesis will contribute to final characterization of this important complex in health and disease.
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36

Kundu, Samit. "Major histocompatibility complex gene diversity in African mole-rats (family : Bathyergidae)." Thesis, Queen Mary, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397312.

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37

Pichowski, Johanna Sara. "Evolution of the major histocompatibility complex class I genes in cattle." Thesis, University of Reading, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389653.

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38

Angus, Rachel. "The expression of major histocompatibility complex antigens by renal cell carcinomas." Thesis, University of Bristol, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385398.

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39

Miltiadou, Despoin. "Characterization of the ovine Major Histocompatibility Complex (MHC) class I genes." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/29891.

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To develop cellular and molecular tools to support development of vaccines against intracellular pathogens of sheep, a molecular genetic analysis of four distinct ovine MHC haplotypes carried by two heterozygous Blackface rams (501 and 504) was conducted. A total of 17 novel sequences was identified, 11 of which were obtained full length. Phylogenetic analysis using the identified transcripts and published ovine, bovine and other ruminant class I sequences belonging to the Bovidae family indicated that there are at least six ovine MHC class I loci (chapter 6). Sequence N1 and N2 are closer to the non classical bovine MHC class I sequence HD15 than to the remaining ovine class I transcripts. Seven out of eight full length transcripts subcloned into a mammalian expression vector expressed detectable class I cell surface glycoproteins in COS-7 cells (chapter 7). The combination of phylogenetic analysis, haplotype, transcription and expression data suggest that there are at least four distinct polymorphic ovine MHC class I loci, three of which appear to be expressed in a number of combinations in individual haplotypes, a couple of non polymorphic poorly transcribed class I like sequences and at least one additional diverged non classical class I locus (chapter 8). Similarities and differences of the ovine MHC class I region with that of other species and implications in immune response and sustainable control of intracellular sheep pathogens are discussed. Using the data generated here, an MHC defined sheep flock, which includes animals homozygous for each of the four MHC haplotypes, is currently under development. The MHC defined resource population, along with the transfected cell lines expressing each of the full length ovine MHC class I sequences, comprise tools for immunization and disease association experiments studying the protective immunity to intracellular pathogens of sheep.
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40

Tarleton, Becky Jean. "Associations of egg production with the major histocompatibility complex in broiler breeder hens." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=716.

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Thesis (M.S.)--West Virginia University, 1999.
Title from document title page. Document formatted into pages; contains vi, 48 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 25-47).
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41

Paxton, Thanai. "Ultra-high sensitivity unambiguous sequencing on a novel geometry quadrupole orthogonal-acceleration time of flight mass spectrometer, the Q-TOF." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322004.

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42

Chrisp, Jacqueline Anne. "Studies on the expression of the IL5 gene in T lymphocytes and the structure and expression of the novel MHC gene G1." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260728.

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43

Lill, Jennie Rebecca. "Characterisation of MHC class I tumour antigens." Thesis, Nottingham Trent University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366082.

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44

Scott, Adrian Phillip. "Investigation of major histocompatibility complex (MHC) associations in sporadic inclusion body myositis." University of Western Australia. School of Pathology and Laboratory Medicine, 2009. http://theses.library.uwa.edu.au/adt-WU2009.0153.

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[Truncated abstract] Sporadic inclusion body myositis (sIBM) is a chronic inflammatory disease that is the most common myopathy in individuals above the age of 50 in the Caucasian population. sIBM is characterised by cytotoxic immune infiltration of skeletal muscle, consisting primarily of CD8+ T-cells and macrophages, as well as a degenerative process, with muscle fibre vacuolation and intracellular filamentous inclusions. The pathogenesis of sIBM is likely to involve a complex interaction between genetic and environmental factors. Whilst the physiological and pathological characteristics of sIBM have been clearly identified, the exact origin and genetic basis of the disease remains unknown. A number of studies show that sIBM is associated with alleles of the major histocompatibility complex (MHC) on chromosome 6p21.3 and specifically with two ancestral haplotypes (AH) in Caucasians – the 8.1AH, defined by HLA-B*0801, HLA-DRB1*0301 and the 35.2AH, defined by HLA-B*3501, HLA-DRB1*0101. Mapping studies subsequently showed that sIBM susceptibility likely originates from a 389kb region of the MHC, spanning from centromeric of PBX2 to telomeric of HLA-DRB1. The central hypothesis of this thesis was that susceptibility to sIBM is conferred by a single allele found within a region defined using the 8.1AH, which is also carried by other haplotypes associated with sIBM. Three patient cohorts from Australia, the U.S.A and Japan were studied. ... Of the 32 alleles genotyped, none were found in all susceptibility haplotypes and one was common, but not unique, to the 8.1AH, 7.2AH and 52.1AH. Five SNPs were also found in two of the three haplotypes, although none were specific to the sIBM susceptibility haplotypes. These data suggest that the 8.1AH is likely to carry an sIBM susceptibility allele independent of the 35.2AH, 7.2AH and 52.1AH. Based on the possible mechanism of action in cellular differentiation and its location within the 8.1AH-defined sIBM susceptibility region reported in 2004, NOTCH4 was a strong candidate for conferring sIBM susceptibility. NOTCH4 coding region polymorphisms were thus investigated in a Caucasian patient cohort to assess any possible role in sIBM susceptibility. While the frequency of some alleles were increased in sIBM patients, the strong linkage disequilibrium throughout the MHC prevented confirmation of any alleles as playing a direct role in sIBM. The 8.1AH-derived sIBM susceptibility region was further refined using recombination mapping. This approach used markers characterised against multiple haplotypes to genotype patients carrying part of the 8.1AH to locate a common, overlapping susceptibility region. Recombination mapping of patients revealed a common overlapping region of the 8.1AH, extending from BTNL2 to HLA-DRB3. The results of the study indicate that 8.1AH-derived susceptibility for sIBM is likely to originate from a 172kb region encompassing HLA-DRA, HLA-DRB3 and part of BTNL2. These genes warrant further investigation in future studies.
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45

Parker, Aimée Dawn. "Classical and non-classical major histocompatibility complex class II genes in the chicken." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607817.

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46

Ono, Santa Jeremy. "Major histocompatibility complex association of insulin-dependent diabetes in the BB rat." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74607.

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BB rats spontaneously develop an insulin-dependent diabetes mellitus strikingly similar to the syndrome observed in man. The disorder requires the presence of multiple susceptibility genes and unknown environmental factors. At least one susceptibility gene resides within the u haplotype of the rat major histocompatibility complex (RT1). Restriction fragment length polymorphism analysis of genomic DNA from rats generated from a series of intercrosses between diabetic BB rats and Buffalo rats (RT1$ sp{ rm b})$ demonstrated that animals heterozygous throughout the RT1 developed IDDM. A single dose of the high risk allele was thus shown to be sufficient for the development of IDDM if other susceptibility factors are present. RFLP analysis of DNA from rats generated in three other breeding studies involving the r8 and r4 recombinant haplotypes mapped the IDDM susceptibility genes between the RT1.A and RT1.C loci, the immune response region. As the u regions of the various haplotypes used in these studies were not derived from the BB rat, the development of IDDM in the progeny strongly suggested that the MHC requirement for IDDM is only for a "u" allele and not a particular or "diabetogenic" u allele.
Analysis of the expression of MHC genes in isolated islets of age-matched BB and Wistar-Furth rats demonstrated enhanced class I MHC gene expression in the islets of prediabetic BB rats. Immunohistochemical analysis confirmed that enhanced class I expression was an early event during the pathogenesis of IDDM, and did not detect aberrant expression of class II antigen on beta cells. Investigation of the inducibility of class I and II MHC genes on the rat insulinoma cell line RIN5F by crude lymphokine preparations or recombinant gamma-interferon indicated that although both classes of genes were inducible, their kinetics of induction are quite different. In vitro nuclear transcriptions demonstrated that induction of the genes had a transcriptional basis. Although class II genes were induced by gamma-interferon, class II antigen was not detected by flow cytometric analysis.
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47

Rosenberg, William. "Immunogenetic studies of the human major histocompatibility complex and T cell receptor." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315822.

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48

Jenkins, David. "Immunogenetic studies of the major histocompatibility complex in insulin-dependent diabetes mellitus." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279926.

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49

Lang, Heather. "T cell receptor crossreactivity with peptide : major histocompatibility complex class II ligands." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418519.

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50

Kirsch, Ralf Dietrich. "Natural killer cell recognition of major histocompatibility complex ligands in the rat." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621888.

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