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The Study Of The Association Of Alzheimer's Disease And Type 2 Diabetes

Posted on:2015-08-20Degree:MasterType:Thesis
Country:ChinaCandidate:Z CuiFull Text:PDF
GTID:2404330491955142Subject:Biophysics
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There is a correlation between Alzheimer's disease(AD)and type ? diabetes(T2D).T2D is one of the AD-inducible factor,the treatment of T2D is apt to cause unreasonable AD.At present while the high proportion of people with both diseases.At the same time there are many similarities T2D and AD pathological features.T2D and AD patients have varying degrees of amyloid deposition phenomenon,have shown varying degrees of damage to the hippocampus,cognitive disorders,and are associated with insulin and insulin resistance.I hope the same study found that over the molecular mechanisms associated with T2D and AD,find the appropriate targets,and research and development while treating the two diseases provide theoretical guidance.AD and T2D are complex disorders,influenced by multiple genes and common environment.Genome-wide association analysis(GWAS)is a powerful tool for the study of complex diseases.Currently scholars for the AD and T2D conducted a number of GWAS.And found a lot of variability associated with the disease locus.Verified and found many disease-related susceptibility genes.APOE gene associated with AD is identified before,and has been validated in GWAS studies on almost all the AD.We also found a large number of susceptibility genes associated with AD,CR1,BIN1,LU,PICALM,MS4A4/MS4A6E,CD2AP,CD33,PHA1 and BCA7.Explain the variation in these genes influence the disease is relatively easy.However,many variable sites in the non-coding region,located in introns or intergenic.Explain the impact of these mutation sites of disease is relatively difficult.In addition,due to the presence of linkage disequilibrium(LD)phenomenon,it is difficult to determine these variable sites,which is the real causative factor.ENCODE project functional DNA elements annotations.Drawn according to the diversity of histone modifications in nine cell lines chromatin state maps,including enhancers,promoters,silencers and heterochromatin and so on.Completed the 125 kinds of cells and tissues of the human DNase I hypersensitive sites(DHSs)whole genome.Using this information,we obtain the mutation sites and the associated GWAS disease were analyzed.DNA functional elements showing different states or functions in different tissues and cell types.When studying AD,select astrocytes cells,including HA-c,HA-sp,Hah,Hah,T2D in the study selection,select islets PanlsletD,PanIslets.Through research and analysis,we obtained several important findings:(1)This paper selected with the AD-related GWAS 27 items with a total of 101 AD highly associated SNPs,use LD 1000 Genomes Project information set r2 0.8 of obtaining 1,661 SNPs.Analysis revealed a total of 34 SNPs located DHSs.(2)subsequently depending on the cell type HA-c,HA-sp,Hah,Hah acquired 64,168 DHSs details.The study found rs47451883,rs105295609,rs99161161 are located chr6:47451880-47452030,chr7:105295520-105295670,chrl3:99161100-99161250.They affect gene RPI1-812120.2,EFCAB10,FARP1,RP11-111L24.3,AL356423.1.(3)This paper selects 29 of about T2D GWAS,a total of 180 SNPs,in accordance with the 1000 Genomes LD information,set parameters r2 0.8 of obtaining 4,167 SNPs,the analysis found that a total of 69 SNPs located DHSs.(4)by mutation sites related to AD and T2D,were analyzed.This paper analyzes found that found that many variable sites,such as rs12721046,rs12721051,rs56131196,rs4420638,rs111789331,rs66626994 not only with Alzheimer's disease,but also with type ? diabetes.In addition GWAS,the 1000 Genomes Project,ENCODE Genome Project and other major plans to produce vast amounts of data,and analysis of these data is still a challenge,the fourth chapter of the data processing methods were studied and analyzed.
Keywords/Search Tags:Alzheimer disease, Type 2 diabetes, SNP, GWAS, ENCODE, DHSs
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