相关资源推荐
作者其它资源推荐
【PDF】精神分裂症候选基因及其病理生理的用户评论&&&免费论文
&&&收费论文
&&&浏览历史上传用户：zzuylztyvk资料价格：5财富值&&『』文档下载 ：『』&&『』学位专业：&关 键 词 ：&&&&&&权力声明：若本站收录的文献无意侵犯了您的著作版权，请点击。摘要:（摘要内容经过系统自动伪原创处理以避免复制，下载原文正常，内容请直接查看目录。）精力决裂症是最多见、最严重的精力性疾病，多发于青丁壮，世界生齿中得病率约为1%；重要表示为精力运动与实际情况想离开、认知、情绪、意志及特性特点等各个方面不调和、互相决裂的疾病。精力决裂症病发重要受情况和遗传两年夜身分影响。家系、双生子及寄养子研讨成果均注解遗传身分在其病发中具有主要感化。精力决裂症基因组扫描和候选基因研讨，虽取得很多阳性成果，但反复性较差，成果争议很年夜。精力决裂症临床症状和认知功效受诸多身分影响，其遗传身分将会备受存眷。目标应用生物信息学、份子遗传学技巧及生物统计学办法，一方面商量DBH、ACE、COMT、DRD2、CHRNA5、IL一10、IL一18、COX一2、TCF4、CACNA1C、MTHFR及GNB1L候选基因上SNPs与精力决裂症联系关系性，另外一方面磨练这些SNPs能否影响受试者临床症状和认知功效，试图提醒精力决裂症易感基因及影响临床症状和认知功效的遗传机制。办法本研讨以350例首发精力决裂症，567例慢性精力决裂症和421例安康对比为研讨对象。精力决裂症患者来自北京回龙不雅病院住院部，正常安康人群来自本地社区。一切研讨对象均为中国汉族人，而且精力决裂症患者要相符ICD一10和CCMD一II一R的诊断尺度。在征得受试者知情赞成的情形下，收集外周静脉血，采取Promega (USA)液体纯化提取DNA试剂盒，提取基因组DNA。应用PCR一AFLP和SequenomMassArray技巧，检测12个候选基因13个SNPs位点（rs、rs4340、rs4680、rs1800497、rs3829787、rs1800872、rs1946518、rs689466、rs5275、rs2958182、rs2239050、rs1801133和rs748806）。运用在线遗传统计SHEsis软件盘算基因型频率散布能否相符Hardy一Weinberg均衡定律；剖析候选基因SNPs位点与精力决裂症的联系关系性；剖析基因各个位点之间连锁不屈衡水平及单倍型；运用MDR软件剖析基因一基因间的交互感化；运用SPSS17。0软件剖析候选基因SNPs位点与精力决裂症临床症状和认知功效的相干性。成果1， H一W均衡磨练和连锁不屈衡水平剖析（1）H一W均衡磨练rs4340、rs3829787和rs5275位点的基因型散布在首发精力决裂症组中偏离H一W均衡；rs1800497、rs3829787和rs1801133位点的基因型散布在慢性精力决裂症组中偏离H一W均衡；解释这些位点能够是疾病易感SNPs位点或与易感SNPs连锁；其他位点基因型散布在首发精力决裂症组、慢性精力决裂症组和安康对比组中均相符H一W均衡定律（all， P＞0。05），解释本研讨抽样样本相符遗传学剖析。（2）连锁不屈衡水平剖析rs689466和rs5275处于高度连锁不屈衡染色体区，解释其位于连锁不屈衡区域内。2，病例一对比剖析(1)首发精力决裂症一正常对比组单个SNP剖析rs和rs5275位点与精力决裂症病发相干联，其等位基因和基因型频率散布在病例组和对比组中均涌现明显性差别（all， P《0。05）。rs2239050和rs3829787位点能够与精力决裂症病发相干联。rs2239050等位基因和rs3829787基因型的频率散布在病例组和对比组中涌现明显差别（both， P《0。05）。(2)慢性精力决裂症一正常对比组单个SNP剖析rs4340、rs1801133和rs748806位点与精力决裂症病发相干联，其等位基因和基因型频率散布在两组中均涌现明显性差别（all， P《0。05）。rs1800497位点能够与精力决裂症病发相干联，其基因型频率散布在病例组和对比组中涌现明显差别（P《0。05）。(3)病例对比组单倍型剖析对COX一2基因的2个SNPs位点停止结合剖析。成果显示，仅rs689466(C)一rs5275(A)作为掩护型单倍型与首发精力决裂症相干联（P《0。05）。3，SNPs与精力决裂症临床症状的相干剖析(1) SNPs与首发精力决裂症临床症状的相干剖析在首发精力决裂症中，DBH基因rs位点和IL18基因rs1946518位点与首发精力决裂症阳性症状和临床症状总分相干（all， P《0。05）；ACE基因rs4340位点与首发精力决裂症阴性症状相干（P《0。05）。(2) SNPs与慢性精力决裂症临床症状的相干剖析在慢性精力决裂症中，COX一2基因rs689466和rs5275位点与慢性精力决裂症的阳性症状相干（both， P《0。05）；TCF4基因rs2958182位点与慢性精力决裂症阴性症状相干（P《0。05）；IL一18基因rs1946518位点与慢性精力决裂症临床症状总分相干（P《0。05）。4，SNPs与认知功效的相干剖析(1) SNPs与正常安康人认知功效的相干剖析在正常安康对比中，TCF4基因rs2958182和CACNA1C基因rs2239050位点与正常安康人认知功效的留意相干（both， P《0。05）；COX一2基因rs5275位点与正常安康人认知功效的说话相干（P《0。05）；TCF4基因rs2958182位点与正常安康人认知功效的延迟记忆和总分值相干（both， P《0。05）。(2) SNPs与首发精力决裂症认知功效的相干剖析在首发精力决裂症中，DBH基因rs、DRD2基因rs1800497位点和COX一2基因rs5275位点与首发精力决裂症认知功效的即刻记忆相干（all，P《0。05）；COX一2基因rs689466位点和rs5275位点与首发精力决裂症认知功效的说话相干（all， P《0。05）。(3) SNPs与慢性精力决裂症认知功效的相干剖析在慢性精力决裂症中，MTHFR基因rs位点和IL一10基因rs1800872位点与慢性精力决裂症留意才能相干（both， P《0。05）；TCF4基因rs2958182位点和MTHFR基因rs位点与慢性精力决裂症的说话才能相干（both，P《0。05）；DRD2基因rs1800497位点和TCF4基因rs2958182位点与慢性精力决裂症认知功效的延迟记忆相干（both， P《0。05）；TCF4基因rs2958182位点与慢性精力决裂症认知功效的总分值相干（P《0。05）。结论从上述剖析可获得以下结论：(1) DBH、COX一2、CHRNA5和CACAN1C基因能够是首发精力决裂症的易感基因；（2）ACE、DRD2、MTHFR和GNB1L基因能够是慢性精力决裂症的易感基因；(3)首发精力决裂症中DBH、IL一18基因和慢性精力决裂症中COX一2基因分离与阳性症状相干（；4）首发精力决裂症中ACE基因和慢性精力决裂症中TCF4基因分离与阴性症状相干；（5）首发精力决裂症中DBH、IL一18基因和慢性精力决裂症中IL一18基因分离与临床症状总分相干；（6）TCF4、CACNA1C和COX一2基因与正常安康人群认知功效功效相干；（7）DBH、DRD2和COX一2基因与首发精力决裂症认知功效相干（；8）MTHFR、IL一10、DRD2、TCF4基因与慢性精力决裂症认知功效相干。（9）精力决裂症存在遗传和临床的异质性。Abstract:Energy break disease is the most common and most serious mental sex disease, multiple in young Ding Zhuang, the world population sick rate is about 1%; important said energy movement and the actual situation to left, cognition, emotion, will and characteristic features, such as the disharmony, each other to break the disease. The energy to break important disease by genetic and two factors. Family, twin and adoption studies were annotated in its genetic element has an important role in the attack. Energy rupture disease genome scanning and candidate gene studies, although there has been a lot of positive results, but the poor repeatability, results dispute is very big. On clinical symptoms and cognitive function break by many factors, its genetic identity will be of concern. Target applications of bioinformatics, molecular genetics and biostatistics method and on the one hand, to discuss the DBH, ACE, COMT, DRD2, chrna5, IL 10 and IL 18, COX 2, Tcf4, cacna1c, MTHFR and GNB1L candidate gene SNPs and energy break disease relationship, also hone these SNPs can be influenced by clinical symptoms and cognitive function, trying to remind energy with schizophrenia susceptibility gene and effect of clinical symptoms and cognitive function of genetic mechanism. Methods in this research, 350 cases of first break energy disease, 567 cases of chronic disease and 421 cases of rupture energy comparison of Ankang as the research object. Energy break patients from Beijing Huilong indecent hospital inpatient department, Ankang normal people from the local community. All the research objects were Han Chinese and energy break patients should be consistent with the diagnostic standard of ICD 10, CCMD II a R. The DNA (USA) was collected from the peripheral venous blood, and the genomic DNA was extracted with Promega (). AFLP and PCR were used to detect 13 SNPs loci (rs4340, rs4680, rs, rs1800497,, rs3829787, rs1800872, rs1946518,, SequenomMassArray,, rs5275,, rs2239050,, rs748806, rs1801133, rs2958182, rs689466). Using online genetic statistics shesis software calculate genotype frequency spread whether conform to hardy Wein analysis of candidate gene SNPs and energy break
analysis between each gene locus linkage Qu Heng horiz the use of MDR software analysis of gene gen by spss17. 0 software to analyze the coherence of candidate gene SNPs loci and energy break clinic symptoms and cognitive function. Results 1, h a w equilibrium hone and chain imbalance level analysis (1) h a w equilibrium hone rs4340, rs3829787 and were rs5275 locus genotypes spread in the starting energy break disease group fr rs1800497, rs3829787 and rs1801133 locus gene distributing in chronic energy break disease group to deviate from t interpretations these sites can be disease susceptibility SNPs or with susceptible SNP other loci spread in the starting energy break disease group, chronic energy break disease group and the healthy comparison group are consistent with h a w balance law (all P & 0. 5), explain the analysis of the sample in the sample. (2) rs689466 and rs5275 are in a high degree of linkage to the chromosome region, which is located in the region of linkage. 2, a case comparison analysis (1) first energy break in the patients with normal contrast group single SNP analysis rs and were rs5275 sites and energy break disease hair related, the bit gene and genotype frequency spread in case group and contrast group were emerging explicit difference (all P & 0. 5). Rs2239050 and rs3829787 were able to break the disease and energy associated disease. The frequency distribution of rs2239050 allele and rs3829787 genotype in the case group and the control group were significantly different (P, both, 0. 5). (2) chronic energy break in the patients with normal contrast group single SNP analysis rs4340, rs1801133 and rs748806 sites and energy break disease hair related. The bit gene and genotype frequency spread in the two groups were emerging explicit difference (all P & 0. 5). Rs1800497 sites can and energy break disease hair related. The genotype frequencies spread the emergence of significant difference (P & 0 in the case group and contrast group. 5). (3) the haplotype analysis of the case group was analyzed by the analysis of the 2 SNPs loci of the gene of COX. The results showed that only rs689466 (C) rs5275 (A) as a cover type and the first break in energy haplotype associated P (&0. 5). 3 SNPs and energy break clinical symptom of coherent analysis (1) SNPs and starting energy break clinical symptom of coherent analysis in the starting energy break disease, DBH gene rs sites and IL18 gene rs1946518 sites and starting energy break and the clinical symptoms of patients with positive symptoms total score of the coherent (all P & 0. 5); ACE gene rs4340 and the first energy break in negative symptoms of coherent (P &0. 5). (2) SNPs and chronic disease clinical symptoms break energy analysis in chronic disease with coherent energy目录:摘要4-8Abstract8-11英文缩写词16-18第1章 前言18-50&&&&1.1 精神分裂症概述18&&&&1.2 精神分裂症患病率和发病率18-22&&&&&&&&1.2.1 发病率18-20&&&&&&&&1.2.2 患病率20-22&&&&1.3 精神分裂症的主要临床症状22-29&&&&&&&&1.3.1 感觉障碍22&&&&&&&&1.3.2 知觉障碍22&&&&&&&&1.3.3 思维障碍22-24&&&&&&&&1.3.4 意志和行为障碍24&&&&&&&&1.3.5 精神分裂症症状新分法24-29&&&&1.4 精神分裂症的临床分型29-30&&&&&&&&1.4.1 单纯型29&&&&&&&&1.4.2 偏执型29&&&&&&&&1.4.3 青春型29&&&&&&&&1.4.4 紧张型29-30&&&&&&&&1.4.5 未分化型30&&&&&&&&1.4.6 残留型30&&&&1.5 精神分裂症的诊断标准30-32&&&&&&&&1.5.1 CCMD 系统30-31&&&&&&&&1.5.2 DSM 系统31-32&&&&&&&&1.5.3 ICD 系统32&&&&1.6 精神分裂症病因与发病机制32-37&&&&&&&&1.6.1 精神分裂症病因32-34&&&&&&&&1.6.2 精神分裂症发病机制34-37&&&&1.7 人类基因组和遗传学标记37-43&&&&&&&&1.7.1 人类基因组的组成38&&&&&&&&1.7.2 人类基因组的结构38-39&&&&&&&&1.7.3 人类基因组 DNA39-40&&&&&&&&1.7.4 遗传标记40-43&&&&1.8 精神分裂症的分子遗传学研究43-50&&&&&&&&1.8.1 精神分裂症的分子遗传研究基本策略43-45&&&&&&&&1.8.2 精神分裂症的分子遗传研究基本方法45-46&&&&&&&&1.8.3 精神分裂症分子遗传学研究进展46-50第2章 材料与方法50-74&&&&2.1 研究对象50-52&&&&&&&&2.1.1 样本来源50&&&&&&&&2.1.2 样本数量50&&&&&&&&2.1.3 首发精神分裂症的入组和排除标准50-51&&&&&&&&2.1.4 慢性精神分裂症的入组和排除标准51&&&&&&&&2.1.5 诊断标准和量表评定51-52&&&&&&&&2.1.6 血液和临床资料收集52&&&&2.2 主要实验试剂、仪器和耗材52-55&&&&&&&&2.2.1 实验试剂52-53&&&&&&&&2.2.2 实验仪器53-55&&&&&&&&2.2.3 实验耗材55&&&&2.3 基因组 DNA 提取、质量检测和浓度标准化55-57&&&&&&&&2.3.1 基因组 DNA 提取55-56&&&&&&&&2.3.2 基因组 DNA 质量检测56&&&&&&&&2.3.3 基因组 DNA 含量和纯度的检测56-57&&&&&&&&2.3.4 基因组 DNA 的稀释和分装57&&&&2.4 选择候选基因和 SNPs57-58&&&&2.5 SNPs 引物设计58-62&&&&&&&&2.5.1 基因序列的获取58-60&&&&&&&&2.5.2 引物设计60-62&&&&&&&&2.5.3 引物稀释及注意事项62&&&&2.6 PCR-AFLP 实验步骤62-64&&&&&&&&2.6.1 PCR-AFLP 技术原理62&&&&&&&&2.6.2 PCR 扩增目的片段62-63&&&&&&&&2.6.3 PCR-AFLP 反应体系63&&&&&&&&2.6.4 PCR 反应循环条件63-64&&&&2.7 Sequenom MassArray 实验步骤64-69&&&&&&&&2.7.1 PCR 扩增反应64-65&&&&&&&&2.7.2 SPA 反应65-66&&&&&&&&2.7.3 延伸反应66-67&&&&&&&&2.7.4 去盐67&&&&&&&&2.7.5 导入 Assay 中67&&&&&&&&2.7.6 样本表格输入67&&&&&&&&2.7.7 建板67&&&&&&&&2.7.8 点样67-68&&&&&&&&2.7.9 Mass Array 分析68&&&&&&&&2.7.10 质量控制68&&&&&&&&2.7.11 输出报告68&&&&&&&&2.7.12 初筛和验证实验中 SNPs 质控68-69&&&&2.8 建立数据库69-71&&&&&&&&2.8.1 Excel 格式数据库69&&&&&&&&2.8.2 TXT 格式数据库69&&&&&&&&2.8.3 SPSS 格式数据库69-71&&&&2.9 统计学处理71-74&&&&&&&&2.9.1 Hardy-Weinberg(H-W)平衡检验71-72&&&&&&&&2.9.2 等位基因和基因型频率计算72&&&&&&&&2.9.3 连锁不平衡（LD）程度分析72&&&&&&&&2.9.4 多位点单倍型分析72&&&&&&&&2.9.5 基因-基因间的交互作用72&&&&&&&&2.9.6 SNPs 与临床症状或认知功能相关性分析72-74第3章 实验结果74-132&&&&3.1 遗传标记的选择74-75&&&&3.2 等位基因和基因型频率75-81&&&&3.3 Hardy-Weinberg（H-W）平衡检验结果81-82&&&&3.4 遗传标记之间连锁不平衡程度的检验82-83&&&&3.5 SNPs 位点等位基因与精神分裂症的关联分析83-90&&&&3.6 SNPs 位点基因型与精神分裂症的关联分析90-97&&&&3.7 病例对照中的单倍型关联分析97-98&&&&3.8 病例对照组的基因-基因交互作用分析98-99&&&&3.9 SNPs 与首发精神分裂症临床症状相关性分析99-105&&&&3.10 SNPs 与慢性精神分裂症临床症状相关性分析105-111&&&&3.11 SNPs 与正常健康对照人群认知功能相关性分析111-118&&&&3.12 SNPs 与首发精神分裂症认知功能相关性分析118-125&&&&3.13 SNPs 与慢性精神分裂症认知功能相关性分析125-132第4章 讨论132-152&&&&4.1 精精神分裂症研究的意义132-133&&&&4.2 精神分裂症研究策略及方法的选择133-134&&&&4.3 候选基因与精神分裂症的关系134-146&&&&4.4 SNPs 与首发精神分裂症的关系146-148&&&&4.5 SNPs 与慢性精神分裂症的关系148-149&&&&4.6 精神分裂症的遗传特点149-152结论152-154参考文献154-184附件184-190作者简介及科研成果190-192致谢192分享到：相关文献|}