VRK2和5-HTTLPR与精神分裂症易感性及脑容量大小相关性的遗传研究传研究
文献类型：学位论文
| 作者 | 王毅 |
| 学位类别 | 硕士 |
| 答辩日期 | 2013-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 宿兵 |
| 关键词 | 精神分裂症 VRK2 5-HTTLPR 大脑容量 相关性分析 |
| 其他题名 | Genetic association analyses of VRK2 and 5-HTTLPR for schizophrenia susceptibility and brain volume variation |
| 学位专业 | 生物工程 |
| 中文摘要 | 精神分裂症是一种以基本个性改变、思维、情感和行为的分裂、精神活动与环境不协调为主要特征的复杂精神疾病。家系、领养及双生子研究证实该疾病具有较高的遗传因素，同时伴有外界环境因素的影响。国内外的学者在精神分裂症易感基因的筛查和定位研究中已获得了很多有价值的结果，但是关于精神分裂症的研究仍然面临很多问题：一个是报道的易感基因在不同群体中无法得到重复；另一个是易感基因的致病机理仍未被阐明。因此，在本论文中我们针对这些问题开展了以下两方面的研究。 首先，我们对在欧洲样本中发现的新的精神分裂症易感基因在东亚人群样本中进行了重复验证实验。2011年来自美国和欧洲的研究小组通过全基因组关联分析（Genome-Wide Association Study, GWAS）报道了一系列欧洲人群中的精神分裂症易感基因，但是这些易感基因在其它人群中的相关性仍然未知。在本研究中我们分析了5个在欧洲样本中达到全基因组水平显著的位点，我们发现其中位于VRK2基因附近的rs2312147在东亚人群与精神分裂症显著相关。我们同时对精神分裂症病人和正常人血细胞中VRK2基因mRNA表达水平进行了分析，结果显示相对于正常人，精神分裂症患者血液中VRK2基因的表达明显上调。我们还分析了rs2312147与脑容量的相关性分析，并发现rs2312147与脑容量和白质体积显著相关，进一步支持了rs2312147在精神分裂症发病和神经系统中的作用。 其次，我们开展了精神分裂症易感位点5-HTTLPR和脑容量大小的相关性分析。据报道精神分裂症患者的大脑容量比正常人的要小，因此有人认为精神分裂症易感基因是通过影响大脑发育而使患者致病的。5-羟色胺转运体(serotonin transporter,5-HTT)是一种位于神经突触前膜的转运蛋白，负责将释放到突触间隙的5-羟色胺转运到突触前细胞。编码该蛋白的基因的启动子区域存在一个插入/缺失的多态性位点（serotonin-transporter-linked polymorphic region，5-HTTLPR）。该多态性位点是一个公认的精神分裂症易感位点，并且已经有研究报道在欧洲人群样本中发现它和大脑容量显著相关。因此，我们想探究5-HTTLPR与中国汉族人群的大脑容量是否也存在这种相关性。结果显示5-HTTLPR和大脑容量没有很显著的相关性。 |
| 英文摘要 | Schizophrenia is a complex human psychiatric disease, with the feature of basic personality change, division of thinking, feeling and behavior, mental activity incompatible with the environment. Family, adoption and twin studies confirmed that the disease has a high genetic factor, accompanied by external environmental factors. Scholars in the field of screening and positioning schizophrenia susceptibility gene have gained many valuable results. However, schizophrenia research is still facing a lot of challenges: one is that the susceptible gene found in one group cannot be replicated in another group; another is that the pathogenic mechanism of susceptible genes has not been elucidated. Therefore, in this project, we have conducted two related studies in order to address the above questions. Firstly, we confirmed the novel susceptible genes found in the European samples. Groups from the United States and Europe reported a series of susceptible genes for schizophrenia by genome-wide association analysis (GWAS), but these susceptible genes need further validations in other samples. In the present study, we performed an association study between the five loci reaching genome-wide significant in the European sample and schizophrenia in Han Chinese sample. Rs2312147 located near the VRK2 gene is significantly associated with schizophrenia. We also compared the mRNA expression level of VRK2 in blood between schizophrenic patients and controls. The results indicated that the gene expression level of VRK2 was up-regulated in patients with schizophrenia. We also analyzed the correlation of rs2312147 and brain volume, and found that rs2312147 was significantly associated with brain volume and white matter volume, further supporting the role of rs2312147 in schizophrenia and central nervous system. Secondly, we conducted an analysis between schizophrenia susceptible locus 5-HTTLPR and brain volume. It is reported that the brain volume of patients with schizophrenia is smaller than that of normal controls, and some people hold the view that schizophrenia susceptible genes exert influence through affecting brain development. 5-HT transporter (5-HTT) is a presynaptic trans-membrane protein responsible for reuptaking the 5–HT released into the synaptic cleft. There is an insertion/deletion polymorphic site (serotonin-transporter-linked polymorphic region, 5-HTTLPR) located in the promoter region of the gene. This polymorphic site is a recognized schizophrenia susceptible locus, and it is reported that this locus is significantly associated with brain volume in the European sample. We therefore tested whether 5-HTTLPR would be correlated with brain volume in Han Chinese population. The results showed that there is no significant correlation between the 5-HTTLPR locus and brain volume. |
| 语种 | 中文 |
| 公开日期 | 2013-05-31 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7447]  |
| 专题 | 昆明动物研究所_比较基因组学 |
| 推荐引用方式 GB/T 7714 | 王毅. VRK2和5-HTTLPR与精神分裂症易感性及脑容量大小相关性的遗传研究传研究[D]. 北京. 中国科学院研究生院. 2013. |
入库方式： OAI收割
来源：昆明动物研究所
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