本文選題：精神分裂癥 + CACNA1I基因��； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景精神分裂癥是一類常見的精神疾病,全球人口患病率高達(dá)1%,給患者及其家屬帶來的沉重的負(fù)擔(dān)與巨大的痛苦。相關(guān)研究表明,精神分裂癥的家族傳遞傾向較高,而風(fēng)險基因的存在對該疾病發(fā)生至關(guān)緊要。精神疾病基因組協(xié)會精神分裂癥工作組(Psychiatric Genomics Consortium-Schizophrenia Workgroup,PGC-SCZ)召集了全球的科研力量開展了這個有史以來精神分裂癥中規(guī)模最大的全基因組關(guān)聯(lián)研究(Genome Wide Association Study,GWAS),這個劃時代的結(jié)果給我們定位了人類精神分裂癥108個易感基因,而鈣離子通道CACNA1I基因也位列其中。近年來Sequenom Mass ARRAY基因分型技術(shù)已成為識別復(fù)雜性遺傳疾病相關(guān)聯(lián)的單核苷酸多態(tài)性易感位點的有效方法,遺傳因素作用的精神疾病應(yīng)用此方法也獲得了眾多珍貴的科研成果。目的PGC-SCZ研究報道的有108個基因位點與精神分裂癥易感,根據(jù)這一研究結(jié)果,探究其中的CACNA1I基因在中國維族人群中是否與精神分裂癥易感。方法本研究對象選取了來自新疆地區(qū)的中國維族人群:正常對照樣本共1218份,精神分裂癥樣本共計985份。Haploview軟件篩選出CACNA1I基因內(nèi)的9個單核苷酸多態(tài)性易感位點,運用Sequenom Mass ARRAY基因分型測序平臺,并對這個9個位點進(jìn)行了分型實驗。各位點的統(tǒng)計分析由強(qiáng)大的SHEsis軟件平臺進(jìn)行處理,包括哈迪溫伯格平衡(Hardy-Weinberg equilibrium)檢驗、等位基因與基因型頻率、單倍型分析等方面。結(jié)果病例對照數(shù)據(jù)表明,共6個位點的等位基因頻率結(jié)果有統(tǒng)計學(xué)意義:rs132575(校正后Pallele=0.039,OR=1.159),rs713860(校正后Pallele=0.039,OR=0.792),rs738168(校正后Pallele=0.039,OR=0.785),rs136805(校正后Pallele=0.014,OR=1.212),rs5757760(校正后Pallele=0.042,OR=0.873)and rs5750871(校正后Pallele=0.039,OR=0.859);同時,rs132575和rs136805兩位點的基因型頻率在病例對照組中的分布差異與精神分裂癥顯著相關(guān):rs132575(校正后Pgenotype=0.037),rs136805(校正后Pgenotype=0.037)。男女分別統(tǒng)計分析后顯示:男性樣本中,有7個位點(rs9607658、rs132575、rs713860、rs738168、rs136805、rs5757760、rs5750871)的等位基因頻率表現(xiàn)出與精神分裂癥顯著相關(guān),有4個位點(rs132575、rs136805、rs5757760、rs5750871)的基因型頻率統(tǒng)計分析后與疾病易感;而所納入的女性樣本中,沒有顯示與精神分裂癥易感的位點。單倍型分析結(jié)果得出,D′值大于0.95的多態(tài)性位點共組成4組單倍型塊(rs132575-rs713860、rs713860-rs738168、rs713860-rs11705208、rs11705208-rs5750871)。對于rs132575-rs713860單倍型塊,單倍型A-T和G-C具有明顯的統(tǒng)計學(xué)意義;rs713860-rs738168單倍型塊中,單倍型C-C和T-A顯示出統(tǒng)計學(xué)意義;rs713860-rs11705208單倍型塊中,單倍型T-C有統(tǒng)計學(xué)意義;在rs11705208-rs5750871單倍型塊中,單倍型C-G和C-A表現(xiàn)出顯著差異。結(jié)論我們的研究結(jié)果表明CACNA1I基因在中國維族人群中是精神分裂癥的一個風(fēng)險因素。此項研究完善了對精神分裂癥致病機(jī)理的探究,也為后續(xù)精神分裂癥發(fā)病通路的研究及抗精神類藥物基因組學(xué)的發(fā)展提供了強(qiáng)有力的支持。
[Abstract]:Background schizophrenia is a common mental disease, the global population prevalence rate of 1%, bring a heavy burden to patients and their families with great pain. Related studies have shown that schizophrenia family transfer tendency is high, and there is a risk of the disease gene crucial. Genome wide association of mental illness the schizophrenia group (Psychiatric Genomics Consortium-Schizophrenia Workgroup, PGC-SCZ) convened a global scientific research strength to carry out the genome-wide association studies in schizophrenia in the largest ever (Genome Wide Association Study, GWAS), this landmark positioning results give us human schizophrenia 108 susceptibility genes. Calcium channel CACNA1I gene is also among them. In recent years Sequenom Mass ARRAY genotyping technology has become related to the complexity of recognition of genetic diseases The effective method for susceptibility loci of single nucleotide polymorphisms associated with the genetic factors of mental disorders using this method can obtain a large number of precious achievements in scientific research. PGC-SCZ reported 108 gene locus and schizophrenia susceptibility, according to the results of this study, to explore whether the CACNA1I gene with schizophrenia easily in Chinese Uygur population. Methods the study objects were selected from the Xinjiang area China Uygur population: a total of 1218 normal control samples, schizophrenia samples for a total of 985.Haploview software selected 9 single nucleotide polymorphism in the CACNA1I gene locus, by typing Sequenom Mass ARRAY gene sequencing platform, and the the 9 loci were divided into experiment. Statistical analysis of the members were processed by SHEsis software platform, including the Hardy Weinberg equilibrium (Hardy-Weinberg equili Brium test), genotype and allele frequencies and haplotype analysis. The results of case-control data show that a total of 6 allele frequency results were statistically significant: rs132575 (Pallele=0.039, OR=1.159), rs713860 (Pallele=0.039, OR=0.792), rs738168 (Pallele=0.039, OR=0.785). Rs136805 (Pallele=0.014, OR=1.212), rs5757760 (Pallele=0.042, OR=0.873) and rs5750871 (Pallele=0.039, OR=0.859); at the same time, some significant difference in the distribution between case and control groups in the genotype frequencies of rs132575 and rs136805 two loci with schizophrenia: rs132575 (adjusted Pgenotype=0.037), rs136805 (after correction Pgenotype=0.037). Statistical analysis showed that men and women were male samples, there were 7 loci (rs9607658, rs132575, rs713860, rs738168, rs136805, rs5757760, rs5750871) allele Because of the frequency significantly associated with schizophrenia, 4 loci (rs132575, rs136805, rs5757760, rs5750871) statistics of genotype frequency analysis of susceptibility and disease; and the women included in the sample, and did not show the schizophrenia susceptibility loci. The haplotype analysis results showed that the value of D 'more than 0.95 polymorphic sites were composed of 4 haplotypes (rs132575-rs713860, rs713860-rs738168 group, rs713860-rs11705208, rs11705208-rs5750871). The rs132575-rs713860 haplotype block, with statistically significant haplotype A-T and haplotype block G-C; rs713860-rs738168, C-C and T-A haplotypes showed statistical significance; rs713860-rs11705208 haplotype block, significant haplotype T-C in rs11705208-rs5750871; haplotype block, haplotype C-G and C-A showed significant difference. Conclusion our results suggest that CACNA1I gene in Chinese Uygur population is a risk factor for schizophrenia. This study has improved the exploration of the pathogenesis of schizophrenia, and has also provided strong support for the follow-up study of schizophrenia pathway and the development of antipsychotic genomics.

【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.3
，

本文編號：1746023