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Screening And Bioinformatics Analysis Of Parkinson’s Disease-related Genes

Posted on:2016-02-22Degree:MasterType:Thesis
Country:ChinaCandidate:G L ChenFull Text:PDF
GTID:2284330482952034Subject:Biochemistry and Molecular Biology
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Parkinson’s disease is common in the elderly degenerative disease of the central nervous system, is the second largest of neurodegenerative diseases, the incidence rate second only to Alzheimer’s disease, Parkinson’s disease pathology is the substantia nigra dopamine neuronal degeneration, the formation of intracytoplasmic Lewy bodies, so that the destruction of the nigrostriatal pathway and the caudate nucleus, putamen decrease in DA content. The main clinical manifestations of resting tremor, muscle rigidity, slowness and gait abnormalities. With awareness of the disease and found that the incidence of PD is increasing year by year the number of the world, coupled with an aging population, and its prevalence is rising. Epidemiological studies abroad show:65 years of age the incidence is 1 to 2 percent, more than 85 years up to 4 to 5% of the total number of people aged over 55 PD patients have more than 170 million people. With the natural aging of our population, the prevalence of PD number increases every year, the number of sick,,has more than two million of its occurrence in a significant geographic and ethnic differences in the region, the highest prevalence in Europe and America, Asia relative lower race, the highest prevalence of white, yellow people, the black people minimum. At present, the most effective treatment for PD is dopamine replacement therapy method, known as PD medication "gold standard", so PD motor symptoms can be effectively controlled, and significantly reduced disability. However, recent studies have found that olfactory dysfunction, sleep disorders, psychiatric disorders, cognitive disorders, and autonomic nervous system dysfunction prevalent in PD patients, and motor symptoms appear at different times, also affects the quality of life of patients. Although not shorten the life of PD patients, but with Alzheimer’s disease, like seriously affect the quality of life of patients, as well as its long duration and high morbidity to patients and families a heavy burden and worry. Therefore, the study of the etiology and pathogenesis of Parkinson’s disease is extremely important.Etiology and pathogenesis of Parkinson’s disease is not clear, now that is a result of the aging of the background, genetic and environmental factors together. Many studies suggest that patients with PD substantia nigra DA neuron degeneration may be associated with mitochondrial dysfunction, oxidative stress, excitotoxicity, neurotrophic factor deficiency, immune dysregulation, apoptosis and a series of mechanisms related links, epidemiological investigation studies have shown that about 10-15% of Parkinson’s patients have a family history. Through the study of the mechanism of genetic factors in the pathogenesis of PD, currently at least a 13 PD cloning of disease genes, suggesting that the incidence of Parkinson’s disease and is closely related to genetic factors, genetic factors and contains multiple genes, multi-factor interactions and affected. Thus the development of Parkinson’s disease research at the molecular level, for its prevention, control and treatment is important.Microarray since the mid-1990s with high-tech molecular biology, the human genome project has developed rapidly, with high throughput, high integration, miniaturization, parallel, diversification and automation features that can parallel, Qualcomm quantitatively detect the expression levels of thousands of gene transcripts, microarray gene expression profiling has been widely used disease find disease-related genes, aspects of drug action boots labeled, prognosis, pathogenesis analysis of complex diseases such as, for individualized diagnosis and treatment guidance, can reveal gene expression and regulation of the relationship between, but it also has an important role in the pharmaceutical and clinical research.Microarray data analysis of qualitative and quantitative analysis is extracted from high-density microarray hybridization lattice points in the fluorescence intensity of hybridization signals through effective screening and related data clustering gene expression profiles, and ultimately integrate hybrid point biological information, found the gene expression profiles and functional link may exist. However, each experiment has produced huge amounts of data, how to interpret the information on the chip hybridization points of thousands of genes, the information data inorganic and organic life activity linked to explain the characteristics and laws of life and functional genes, biological information learn important research topic. Analysis of microarray data, including pre-experimental design, data pre-processing and post-detailed analysis of other steps.Microarray provides vast amounts of information, including gene function, gene interactions, and these data for functional genomic studies provide important resources, GEO, SMD, ArrayExpress and other databases in microarray classification, storage, sharing of resources, such as providing favorable assistance. Data is an important source of knowledge and information, and can not be done by a simple calculation and analysis of these data have, therefore, how to use some new methods and techniques to effectively analyze these massive gene chip, and from mining and reveal hidden meaningful biological information is an important topic in the field of the current gene chip solved.Bioinformatics is accompanied by the development of the human genome program generated an involving biology, mathematics and computer science and interdisciplinary. Bioinformatics is the integration of the emerging discipline of life sciences and mathematical sciences, specifically bioinformatics are nucleic acids, proteins and other biological macromolecules database as the main object of study, mathematics, information science, computer science major research tools, computer hardware, software, and computer networks as the main research tool for vast amounts of raw data storage, management, annotation, processing. Making the biological information with a clear biological significance. And through bioinformatics query, search, comparison, analysis, derive gene encoding, regulation, and protein structure and function of biological knowledge and relationships to explore the origins of life on the basis of large amounts of information and knowledge, as well as cell biological evolution, life sciences major problems occur organs and individuals, development, disease, aging, etc., to find out the basic rules and temporal linkages between them.With the recent development of the biological test methods and test data, and accumulated a lot of biology, especially molecular biology experimental data by the data classification, collection, sorting, resulting in thousands of databases. In order to efficiently deal with the growing mass of biological data, allowing researchers around the world to share existing research results, database technology in the processing and storage of biological data, there are more important applications. Database is the main content of bioinformatics, various databases covering almost all areas of life sciences. Common nucleic acid and protein databases such as NCBI nucleic acid sequence databases, protein databases (UniProt), etc; microarray databases, such as high-throughput gene expression database (GEO); disease-related databases, such as GeneCards (gene card), drugs and disease database (DrugBank) and the like. Currently, bioinformatics has been widely infiltrated into all areas of life science research, and become an indispensable tool in the discovery of human disease genes and functions, function research to identify genes and proteins play a key role such as drug design, gene polymorphism analysis, gene regulation, the identification of disease-related genes, gene products structure and function prediction, gene evolution, epidemiology, genetic research genetic mechanisms of cancer and so on.In this study, GEO database of gene expression data analysis on Parkinson’s disease for the material, the use of filtering software Qlucore Omics Explorer3.0 differences in gene expression GSE22491 by DAVID, KEGG, STRING, etc. online analysis software for differential gene bioinformatics analysis, to provide a meaningful basis for exploration and molecular pathogenesis of Parkinson’s disease, drug development and treatment.After filtering criteria set according to the value and the median normalized, QOE3.0 software to identify a total of 1752 differentially expressed genes, which raised 1561, down 191. Showed major differentially expressed genes involved in protein translation, translation elongation, metabolic precursor messenger ribonucleic acid metabolic process, the electron transport chain, RNA and mRNA modification, the ubiquitin-proteasome-dependent protein catabolism by DAVID promote biological process analysis ubiquitin protein ligase for negative regulation of mitotic cell cycle, etc; molecular function showed differentially expressed genes mainly involved structural component of the ribosome, RNA complexes, active structure of the molecule, the role of redox on NADH or NADPH activity, NADH dehydrogenase activity, hydrogen ion transmembrane transport activity, oxidoreductase activity, acting on NADH or NADPH quinone or similar compound receptors, transmembrane cation transport activity and the like. By KEGG analysis, these differences genes mainly involved in ribosome signaling pathway, Parkinson’s disease signaling pathway, oxidative phosphorylation signaling pathways, signaling pathways Huntington’s disease, Alzheimer’s disease signaling pathway, proteasome signaling pathways, cardiac muscle contraction signal path oocyte meiosis signal, the signal path Vibrio cholerae infection, leukocyte transendothelial migration signaling pathway, the pentose phosphate pathway signaling pathway, citric acid signaling pathway, FcyR-mediated phagocytosis pathway, etc.Obtained by further filtering software QOE3.0101 differentially expressed genes is relatively large, these 101 genes STRING uploaded to online tools to analyze the interaction between the proteins encoded by these genes, the results show that the entire network to SKP2, ACTC6A, RBX1, BUC, SMARCD1, SKP1, CUL1, BTRC, SMARCC1, SMAPCA4, CDK2, CUL4A, TAF4, CTNNB1, FBXW11 protein with other proteins>10 interaction exists between, for the central node of the network of protein interactions, protein delete these nodes after the network structure lax. These genes in the development of the role of different cancers have been reported, which SKP2, RBX1, SKP1, CUL1, CUL4A ubiquitin proteasome has close links, the ubiquitin-proteasome may play an important role in the pathogenesis of PD these genes may also be used as a potential therapeutic target PD. These genes are miRNA-30b, miRNA-30c, miRNA-26a,target gene and the three miRNA in neurons and glial cells, indicating that the three miRNA may be apotential biomarker for Parkinson’s diseaseIn summary, this study bioinformatics to analyze a set of data PD-related genes, and provide a reference for further experimental research will help guide further research in PD.
Keywords/Search Tags:Parkinson’s disease, Gene chip, Bioinformatics, Differential genes, protein-protein interaction, miRNA
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