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Bioinformatic Analysis Of Genes Related To Type 2 Diabetes Mellitus

Posted on:2016-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:Z H LiFull Text:PDF
GTID:2284330482956626Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Diabetes mellitus (Diabetes mellitus, DM) is one kind of endocrine and metabolic diseases, determined by genetic factors, environmental factors and behavioral factors which are characterized by hyperglycemia. The main pathogenesis of diabetic is insulin resistance and impaired beta cell. The decrease secretion of insulin caused the disorder of glycometabolism, making blood sugar too high. The mainly manifested symptoms of diabetes are polydipsia, polyphagia, polyuria, weight loss and other symptoms. Diabetes is always classified as four types:type 1 diabetes mellitus(T1DM), type 2 diabetes mellitus (T2DM), gestational period diabetes and other types of diabetes. Although each type of diabetes symptoms are similar sometimes are same, the cause of the disease and their distribution in different populations are different. Every type of diabetes will lead to the damage of pancreatic beta cells that cannot produce enough insulin to reduce the blood glucose concentration, which will lead to the occurrence of hyperglycemia. Type 1 diabetes is also known as insulin-dependent diabetes. The autoimmune system is broken generally due to the destruction of insulin producing beta cells causes, mostly occurred in children and adolescents. Type 2 diabetes mellitus is also known as non-insulin-dependent diabetes mellitus, due to tissue cells insulin resistance, caused the decline in beta cell function or a variety of other reasons, mostly occurred in adults and the elderly, and above 95% diabetics were type 2 diabetes. Gestational diabetes mellitus is similar to type 2 diabetes, but the insulin resistance is due to the hormone of pregnancy women (hormone) secretion. The other types of diabetes is the types except type 1, for type 2 and gestational diabetes including diabetes caused by pancreatic disease, diabetes caused by endocrine diseases, genetic disease accompanied with diabetes and drug induced diabetes, etc. Other diabetes has many kinds, but patients are far less than the type 2 diabetes.With the rapid development of social economy, urbanization has been greatly improved, people’s physical labor intensity was obviously reduced, sedentary work style significantly increased, life has changed a lot, high calorie diet were increased, and the population aging of many countries were increased, the prevalence and the incidence of diabetes are increasing. According to the International Diabetes Federation Statistics (IDF) statistics, patients with diabetes were about 100 million in twentieth Century 90 years worldwide, and the number is 246 million in 2007, it is expected that by 2025, the number of diabetic patients in the world will be increased to 380 million. Diabetes has become a public health problem in the world in twenty-first Century.According to the national survey shows of Chinese Diabetes Society in the 2010, China has about 92.4 million adult diabetes patients currently, Chinese diabetes prevalence rate has increased from 0.67% in 1993 to 3.21% in 1980. Our country has change from low prevalence rate of diabetes nation to medium prevalence rate of diabetes nation in less than 20 years. At present, the total number of diabetic patients in China is second in the world, just behind India, and has become the world’s diabetes epidemic center. Because diabetic patients need long-term treatment, and suffered with a variety of complications, and the patients with diabetes bear a heavy economic pressure. According to diabetes treatment costs of China’s statistics, the cost of diabetes treatment was more than the gross national product (GDP), in 2004 has reached 19.9%, and has became the highest in second chronic diseases. Type 2 diabetes and its complications not only brought great pain to patients, but also brought enormous economic pressure and social pressure to our country.More than 90% of the diabetic patients in the world were type 2 diabetes. To find effective measures to control and reduce the incidence of diabetes, the key is how to effectively control the incidence of type 2 diabetes. Type 2 diabetes is caused by joint action of genetic factor and environmental factor, and its pathogenesis is still not completely elucidated. But now that insulin resistance and insulin secretion are two basic factors in the pathogenesis of type 2 diabetes mellitus. Type 2 diabetes is very subtle in its early onset, and the incubation period can reach 9-12 years. There is no obvious clinical symptoms in the early stages in a large part of patients after diagnosis, and the brain, heart, eye, kidney and other important organs complication has emerged, which also led to the main reason sugar urine sickness disability and illness rates remain high both of the patients themselves, or brings a great burden to their family. Therefore, the method for prevention and treatment of type 2 diabetes mellitus is a difficult problem that is urgent in medical staff and researchers.Gene chip (gene chip), also known as the DNA chip (DNA chip), DNA microarray (DNA microarray), oligonucleotide microchip (oligonucleotide microchip), was one kind of biochips, which was development of "human genome project" (human genomic project, HGP) and the implementation of molecular biology. The gene chip was one of the most important technology in the twenty-first Century life science. This technology is an effective method for screening differentially expressed genes, which has the advantages of high through put and fast measurement. Gene expression profiling refers to the non bias cDNA Library in a cell or tissue in a particular state of the construction of the large-scale cDNA sequencing analysis of the mRNA group, composed of collection of cDNA sequence fragments, so as to describe the specific cell or tissue in a particular state of the gene expression type and abundance information, so the preparation of a data table is called gene expression profile. With the expression microarray technology extensively, produced rich, massive, complex biological information data. How to read the tens of thousands chip genes hybridization information, revealing the characteristics and rules of life, which has became the main "bottleneck restriction of gene chip technology application and development".Bioinformatics (Bioinformatics) was developed with the human genome project (Human genome project) in 1980s, a new frontier science and information science that has become through modern biology and Medical Science (such as biochemistry, cell biology, developmental biology, genetics, genomics, physiology computer science, biostatistics, mathematics etc). It revealed the biological meaning contained in the data through the biological experimental data acquisition, processing, storage, retrieval and analysis. The content of the research included the sequence and structure alignment, protein structure prediction, gene identification, molecular evolution analysis, comparative genomics, sequence, gene expression profiles of drug design, etc. In many current research, involving the using of a bioinformatics to study the disease.This research is mainly divided into the following three parts:The first part:the obtain of the gene chip of organization of islet in type 2 diabetes:the expression data of a group of related and islet tissue of type 2 diabetes genes was used in this study, which was downloaded from GEO of National Center for Biotechnology Information America (NCBI) database, searched with "diabetes, type diabetes mellitus 2" as the key words in the GEO Datasets database search box. We obtained the GSE25724 chip data submitted by Bugliani M, and the experimental platform is HG-U133A chip of Affymetrix company. A total of 13 samples, including 6 cases of pancreatic tissue of type 2 diabetic samples,7 samples are normal islet tissue.The second part:A comprehensive analysis through the Qlucore Omics Explorer, Panther, David and other bioinformatics software:the expression of 13 gene chips through using Qlucore Omics Explorer (normal type 2 diabetes islet tissue of 6 cases of samples and normal islet tissue samples from 7 patients) analysis, and obtained 782 differentially expressed genes between type 2 diabetes and normal tissue pancreatic islet tissue, including 41 genes up-regulated,741 down-regulated genes. Through the comprehensive analysis of differentially expressed genes of DAVID, PANTHER, GATHER, we found that differentially expressed genes function mainly in cell apoptosis, immune process, stress reaction process in the biological process. In the cell fractions, differentially expressed genes function mainly in cell membrane, cell membrane, ribosomal protein etc. In molecular function, the function of differentially expression genes mainly concentrated in the nucleotide binding, the ATP binding, enzyme regulator activity, protein transport activity.In the passage the differentially expressed genes were enriched mainly in the following pathways:tri-carboxylic acid cycle pathway, pyruvate recycling pathway, fat metabolism pathway, pathway of apoptosis, wnt signaling pathway, P53 signal pathway, oxidative stress response pathway, insulin signaling pathway and TGF-beta signaling pathway signaling pathways. The important significance pathways were three carboxylic acid cycle signal pathway and insulin signaling pathway.The third chapter:building a network of protein and protein interaction:we use Cytoscape to construct the protein interaction network, and get PPI to construct protein interaction network diagram by Cytoscape. Through calculating the average degree of node degree and all nodes on the network diagram, we get greater than or equal to 6 times the average node degree of all nodes. The core protein was ANAPC10, LAMTOR5, YWHAQ, UBE2D2, RRAGA and RRAGD. These proteins are crucial proteins in the ppi network in type 2 diabetes mellitus.
Keywords/Search Tags:Type 2 diabetes, Gene chip, Bioinformatics, Differential genes, protein-protein interaction
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