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Preliminary Study Of The Differences In DNA Methylation Between Multiple Sclerosis And Neuromyelitis Optica

Posted on:2017-12-08Degree:MasterType:Thesis
Country:ChinaCandidate:J J ZhaoFull Text:PDF
GTID:2334330488970654Subject:Neurology
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Object: Through the whole genome DNA methylation detection of peripheral blood to the patients who are diagnosed with Multiple Sclerosis(MS)and Neuromyelitis Optica(NMO)to investigate whether there are some differences in the status of the NDA methylation between these two kinds of illnesses.Methods: Select 4 patients respectively who are clinically diagnosed with MS and NMO,and keep their blood samples.At the same time,select 4 patients respectively whose age and gender are matched with the above patient.Also keep their blood samples as a Control Group.Then extract the DNA from the samples,check the status of the whole genome DNA of these 3 groups by using the Experimental method of Human Methylation 450 methylation chip and compare with one another,then use the unsupervised hierarchical clustering method to the differential methylated sites.Finally calculate the direct relations of the samples of the samples with the expression of the selected differential methylation sites.Use differential integration analysis to search for the 3 groups of common or specific differentially methylated sites.And then GO analysis and KEGG pathway analysis are used to reveal the functions of these differentially methylated sites and the cell pathway.Search MS or NMO-ralated references,to find out that what cell pathway changes are probably ralated to the different sample differential gens and are involved in the disease control and reguation of cellular pathways.Results:1.There are respectively 208?639 and 4309 DNA differential Methylated sites in Group MS and Group C?Group NMO and Group C?Group MS and Group NMO.And DNA methylation level between the three groups exist significant difference(??>0.17?<-0.17,P<0.05).There are 5 DNA Methylation sites whose methylation level are statistically significant,and they are the common difference between the 3 group.2.Allograft rejection,excracellular matrix receptor interactions(ECM-receptor interaction)cell adhesion factor,cell adhesion moleculos and cams and other cellular,pathway may be involved in the pathogenesis of MS.3.AMPK signaling pathway,Fc gamma R-mediated,phagocytosis,cholinergic synapse and other other abnormal cell pathways may be involved in the pathogenesis of NMO.4.The abnormal pathways of AMPK signaling,rap1 signaling,B cell receptor signaling pathway,Cholinergic synapse and so on may have involved in the pathogenesis that are probably different between MS and NMO.Conclusions:1.Human whole genome DNA methylation chip is successfully used in the analysis of the differences of the peripheral blood DNA methylation among the patients who are diagnosed with MS?NMO and the normal people.2.The detection of methylation in peripheral blood has a certain guiding meaning for the diagnosis and treatment of MS and NMO.3.The 2 diseases' different pathogenesis are revealed from the perspective of epigenetics.4.The abnormalities of DNA methylation may affect the expression of the corresponding genes,and then cause come changes in the pathways of cell functions,and participate in the MS and NMO pathological process.
Keywords/Search Tags:DNA, methylation, MS, NMO, Demyelination, Epigenetics
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