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Study on SNPs in HLA-Ⅱ Family of Patients with Rheumatoid Arthritis

Author: WangHua
Tutor: QiMing
School: Jiangsu University
Course: Clinical Laboratory Science
Keywords: Rheumatoid arthritis HLA-II family single nucleotide polymorphism (SNP) bioinformatics PCR-SSP
CLC: R593.22
Type: Master's thesis
Year: 2009
Downloads: 182
Quote: 1
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Abstract


Background:single nucleotide polymorphism(SNP) is defined as single base sequence disparity of genome DNA in certain colonia or normal individuals,which is the simplist and most extensive polymorphic type in genome of biosystem.Over 90%of the essential qualities reflection on genetic information of human gene polymorphism was due to SNPs characterized as extensive distribution,large quantity and relative stability.The occurrence of SNP may lead to the change of protein sequence or conformation and SNP is considered to be critical to human body constitution resulting in individual variation in liability to certain disease and reaction to certain treatment.The research of SNP is now focused on the coding sequence SNP(cSNP) which is classified as synonymous cSNP and non-synonymous cSNP according to whether the mutational base contributing to the change of amino sequence.Nowadays, researcheres are making great efforts in the exploration of the background of human disease-associated genes,SNP become a hot spot due to its advantages in heredity research.Rheumatoid arthritis(RA) is one of the most frequent autoimmune disease,its high attack rate and irreversible joint damage in advanced stage greatly influence the life quality of patients and result in large expense of human resources and financial resources.To explore the genetic background of RA help to understand the pathogenesy and is benefical to the diagnosis and treatment of the disease.Human Leukocyte Antigen(HLA) system is human major histocompability complex,with tight association with immunologic mechanism and copious polymorphism.HLA is an important target domin in reserch on genetic background of immunological disease.HLA-DRB1 and DQB,whose allele with richest polymorphism in HLA-Ⅱfamily,is associated with the occurrence of rheumatoid arthritis,but whether their SNPs are related to rheumatoid arthritis is still unknown.In order to explore the relationship between SNPs and rheumatoid arthritis,we analyzed the genetype frequency through testing SNPs of HLA-DRB1 and DQB,anticipated to find out RA associated SNPs.Methods:we used bioinformatic methods in SNP screening of the HLA-DRB1 coding regions and referred to related report;selected 11 potential desease-associated SNPs and classified them into 3 groups to make further indentification in clinical.30 patients were selected according to the diagnostic criteria of rheumatoid arthritis,and 30 healthy persons were used as control.Venous blood was obtained and DNA was extracted by Phenol-chloroform method,genetype frequency of 11 SNPs was analyzed by PCR-SSP.Results:the coding region of HLA-DRB1 gene contained 113 non-synonymous cSNPs,and 3 of them(rs1059576、rs1059582、rs 1059586) may contribute to detrimental mutation through bioinformatic analysis.Further test suggested the potential detrimental 3 SNPs were no associated with rheumatoid arthritis,other 4 SNPs selected by chance showed no statistical significance either.2 SNPs of NOTCH4 gene(rs2071282、rs2071283) were associated with rheumatoid arthritis.rs1049110,the SNP we selected in DQB2 gene,showed no statistical significance.Conclusion:No SNPs in HLA-DRB1 gene were found to be associated with rheumatoid arthritis,suggesting further research should be made to clarify the role in the occurrence of rheumatoid arthritis.2 SNPs in DQB gene were related to rheumatoid arthritis.

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Rheumatoid arthritis
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