本文選題：精神分裂癥 + 單核苷酸多態(tài)性��； 參考：《南昌大學》2013年碩士論文

【摘要】：一項由Lewis等進行的大型精神分裂癥患者全基因組連鎖掃描的薈萃分析顯示6p22.3-21.1為精神分裂癥的連鎖區(qū)域[1]，MDGA1位于6p21.2，病例-對照研究表明MDGA1基因為精神分裂癥易感基因之一。為探討MDGA1基因是否為中國漢族人群精神分裂癥的風險基因，本研究以核心家系為研究對象，，分析MDGA1基因多態(tài)性與中國漢族精神分裂癥患者的關聯(lián)。 研究共選擇36個江西漢族精神分裂癥核心家系為研究對象，共108例。選取目標基因MDGA1上6個單核苷酸多態(tài)性位點（single nucleotide polymorphisms,SNPs）：rs6900617、rs11759115、rs7769372、rs9462341、rs12191311及rs804831。利用多重聚合酶鏈式反應（Multiplex PCR），多重連接酶檢測反應（Multiplexligase detection reaction，Multiplex LDR）技術檢測個體基因型。運用擬合優(yōu)度x2檢驗檢測各位點基因型頻數(shù)是否符合Hardy-Weinberg平衡，使用家系的關聯(lián)分析軟件（Family BasedAssociatin Test，F(xiàn)BAT）2.0.4版本，進行MDGA1基因多態(tài)性與精神分裂癥的傳遞不平衡檢驗（Transmission disequilibrium test，TDT）和單倍型相對風險檢測（haplotype relative risk，HRR）。 MDGA1基因上6個SNP位點基因型分別在健康父母組及患病組中進行Hardy-Weinberg平衡檢驗，患病組中位點rs6900617和rs7769372χ~2分別為6.506和3.992，均顯示出統(tǒng)計學差異（P0.05），即不符合Hardy-Weinberg平衡。除此兩位點外，其余四位點及健康父母組各位點均符合Hardy-Weinberg平衡檢驗；各等位基因及基因型頻數(shù)分布分析結果得出，rs9462341與女性精神分裂癥相關聯(lián)（χ~2=4.125，df=1，P0.05）；rs12191311、rs11759115、rs804831及rs9462341四位點進行單個位點TDT檢驗和HRR分析，結果顯示在可加模型，隱性模型下，遺傳標記位點rs9462341與精神分裂癥關聯(lián)，等位基因T過多傳遞，為精神分裂癥的危險因素， P值分別為0.015777和0.005960，差異有統(tǒng)計學意義；顯性模型下，等位基因A與精神分裂癥提示關聯(lián)（P=0.005960），其對應的Z值為-2.750，等位基因A為精神分裂癥的保護因素，位點rs9462341在核心家系中顯示出傳遞不平衡性；而rs12191311、rs11759115及rs804831的TDT檢驗P值均大于0.05，表明此三位點與精神分裂癥無關聯(lián)。rs12191311-rs11759115-rs804831-rs9462341中的C/T/T/A的單倍型與精神分裂癥相關，其P值為0.049861，對應的Z值為-1.961，提示C/T/T/A為精神分裂癥的保護因素。其余各單倍型與精神分裂癥均未顯示出關聯(lián)（P＞0.05）。 結論： 1. MDGA1基因rs9462341位點與精神分裂癥相關聯(lián)(P0.05)，等位基因T過多傳遞，為精神分裂癥的危險因素，等位基因A為精神分裂癥的保護因素； 2. rs12191311-rs11759115-rs804831-rs9462341組成的C/T/T/A的單倍型與精神分裂癥關聯(lián)(P0.05)； 3. MDGA1基因rs9462341位點與女性精神分裂癥相關聯(lián)。 4. MDGA1基因位點rs11759115、rs12191311和rs804831與精神分裂癥無關聯(lián)； 5. MDGA1基因可能是中國漢族人群精神分裂癥患病基因。
[Abstract]:A meta-analysis of the whole genome linkage scan of large schizophrenic patients by Lewis et al showed that 6p22.3-21.1 was a linkage region of schizophrenia [1] and that MDGA1 was located at 6p21.2. A case-control study showed that the MDGA1 gene was one of the susceptible genes for schizophrenia. In order to investigate whether MDGA1 gene is a risk gene for schizophrenia in Chinese Han population, this study analyzed the association of MDGA1 gene polymorphism with schizophrenia in Chinese Han nationality. A total of 36 nuclear families of Jiangxi Han nationality with schizophrenia were selected as subjects. Six single nucleotide polymorphisms SNPs: rs6900617, rs11759115, rs7769372, rs9462341, rs12191311 and rs804831 were selected from the target gene MDGA1. Individual genotypes were detected by multiplex polymerase chain reaction (PCR) and multiplex ligase detection reactionation multiplex (LDR) technique. Using the goodness of fit x2 test to test whether the frequency of genotypes at each point conforms to the Hardy-Weinberg balance, and using the family association analysis software, Family BasedAssociatin Test / FBAT2.0.4, Transmission disequilibrium test of MDGA1 gene polymorphism and schizophrenia was performed to detect the relative risk of transmission disequilibrium test and haplotype relative. Six SNP loci genotypes of MDGA1 gene were tested for Hardy-Weinberg balance in healthy parent group and disease group respectively. The median rs6900617 and rs7769372 蠂 ~ 2 were 6.506 and 3.992, respectively, which showed statistical difference (P 0.05), which was not in accordance with Hardy-Weinberg balance. With the exception of these two loci, the other four loci and the healthy parent groups all met the Hardy-Weinberg balance test. The analysis of frequency distribution of alleles and genotypes showed that rs9462341 was associated with female schizophrenia (蠂 ~ 2 / 2 = 4.125). The results showed that rs1219131111rs11759115rs804831 and rs9462341 four loci were tested by single locus TDT and HRR analysis, the results showed that, under additive model, recessive model, and recessive model, RS9462341 was detected by single locus TDT test and HRR analysis. Genetic marker locus (rs9462341) was associated with schizophrenia. Allele T was transmitted too much and was a risk factor for schizophrenia (P = 0.015777 and P = 0.005960, respectively). Allele A was associated with schizophrenia. The Z value of allele A was -2.750. Allele A was the protective factor of schizophrenia. The rs9462341 locus showed transmission imbalance in nuclear families. The TDT test P values of rs121913111rs11759115 and rs804831 were all greater than 0.05, which indicated that the haplotypes of C/T/T/A in rs12191311-rs11759115-rs804831-rs9462341 were related to schizophrenia, P = 0.049861and Z = -1.961respectively, indicating that C/T/T/A is the protective factor for schizophrenia. The other haplotypes were not associated with schizophrenia (P > 0.05). Conclusion: 1. The rs9462341 locus of MDGA1 gene was associated with schizophrenia (P 0.05). The allele T was transmitted too much, and allele A was the protective factor of schizophrenia. 2. Haplotype of C/T/T/A composed of rs12191311-rs11759115-rs804831-rs9462341 was associated with schizophrenia (P 0.05); 3. The rs9462341 locus of MDGA1 gene is associated with schizophrenia in women. 4. MDGA1 locus rs11759115 rs12191311 and rs804831 were not associated with schizophrenia. 5. MDGA1 gene may be a gene of schizophrenia in Chinese Han population.
【學位授予單位】：南昌大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R749.3

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相關期刊論文 前1條

1 潘發(fā)明;夏果;廖芳芳;葛銳;梅楊;鄒延峰;范引光;;復雜疾病家系關聯(lián)性分析FBAT軟件簡介[J];中國衛(wèi)生統(tǒng)計;2009年04期

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