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A Genome-Wide Association Study of Sporadic Amyotrophic Lateral Sclerosis in Chinese Han Population

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Tutor: XuRen
Course: Neurology
Keywords: Chinese han people,Sporadic Amyotrophic lateral sclerosis,genome-wide associatio
CLC: R746.4
Type: Master's thesis
Year:  2013
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Objective:Amyotrophic lateral sclerosis is one of motor neuron diseases, the pathogenesis isnot understood clearly. But genetic factor may play an important role in the disease.Genome screening is an effective way to discover new gene. Europeans and Americanshave find some accoaited genes in prelimnary studies. Hence, we have conducted agenome-wide association study(GWAS) in Chinese Han people, to discover whetherthese are some different genes between Chinese Han people and Europeans andAmericans.Methods:The clinical dates and peripheral venous blood of200cases of confirmed sALSand200controls of healthy were collected, extracted the genomic DNA, then DNA wasmixed with an equal amount of each test subgroup to construct casesand controls DNAmixed pools, using SNP chip to conduct a high-density SNPs hybridization, throughcomparative SNPs allelic frequency to determine whether they are significantdifferences or not.Results:The mean age at oneset of200cases was48.5±8.4years, onset before40yearsand after80years was less. Male to female ratio was1.5:1. The mean age at oneset of200controls was59.8±11.6years. Male to female ratio was1.3:1; Through thequality control,859311SNPs have information of genes interpretation,12670SNPshave no information of genes interpretation;③Discover new susceptibility genes ofsALS: INPP5B (kgp15327256),IQCF5/IQCF1(rs1605070),ITGA9(rs9825420),LOC727878/PFKP (rs9329300), MYO18B (kgp8087771), LOC100287880/ALCAM(rs2685056),LOC100128095/OPCML(rs7117082),GPR133(rs11061269).④Pathway analysis found that three pathways contain361genes may be related withthe sALS.Conclusions:After GWAS with gene chip scanning、data analysis and pathway analysis using DNA pooling.,8suspicious SPD susceptibility genes,3pathway and361associativegenes were found. We the Chinese han people may be have the different sALSsusceptibility genes from people who came from Europe and the United States. Thismay play an important role for the further sALS research on mechanism.
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