| 1 | int。J. Neuropsychopharmacol。2009年8月12日：885-94 |
|---|---|
| PMID | 19154657 |
| Title | Association between golli-MBP and schizophrenia in the Jewish Ashkenazi population: are regulatory regions involved? |
| Abstract | 多项研究报道了少突胶质细胞和髓磷脂异常，以及其相关基因失调，精神分裂症患者。这些基因之一是髓鞘基蛋白（MBP）基因，该基因编码了两个蛋白质家族：经典Mbps和Golli-Mbps。尽管经典Mbps主要位于神经系统的髓鞘中，但Golli蛋白的表达更广泛，并且在免疫系统和神经系统中都被发现。在本研究中，我们在两个独立的犹太人Ashkenazi队列中对Golli-MBP进行了病例对照关联分析（队列I：120名患者，236例对照；队列II：379名患者，380例对照）。此外，我们在尸体后外侧前额叶前额叶皮层样品中对Golli-MBP mRNA进行了表达分析精神分裂症患者和匹配的对照。在第一个队列中，我们观察到6个（在26个基因分型）单核苷酸多态性（SNP）和疾病之间的关联（P <0.05）。其中，三个来自一个链接不平衡（LD）块，其中包含一个CTCF结合区域。单倍型分析显示出明显的“风险”/“保护性”单倍型（最强的P = 0.005，每个）精神分裂症。然后在第二个队列中对三个SNP（RS12458282，RS2008323，RS721286）进行了基因分型。合并的结果在单个标记和单倍型分析中表现出强烈的影响（最强或1.77，p = 0.0005;或分别为1.61，p = 0.00001）。测序CTCF结合区域揭示了与相关的单倍型完整LD中的三个SNPCTCFbinding site. Expression analysis found no significant differences in golli-MBP mRNA levels. These findings suggest that golli-MBP is a possible susceptibility gene for精神分裂症。 |
| SCZ Keywords | 精神分裂症 |
| 2 | PLoS ONE 2011 -1 6: e18455 |
| PMID | 21494683 |
| Title | Genetic and metabolic characterization of insomnia. |
| Abstract | 据报道，失眠症会慢性影响10％的成年人口。但是，关于失眠的遗传学和代谢知之甚少。在这里，我们调查了10,038名韩国受试者，其基因型以前已经以全基因组量表进行了介绍。约有16.5％的人报告失眠，并显示出明显的代谢变化，反映了胰岛素分泌的增加，糖尿病的风险较高以及钙信号破坏。与失眠相关的基因型差异高度集中在参与神经功能的基因中。最重要的SNP属于ROR1和PLCB1，已知与双相情感障碍和精神分裂症， 分别。如组蛋白标记H3K4ME1所示，在显着SNP附近的两个基因中都发现了假定的增强子。在神经元细胞中，增强子由PAX6结合，PAX6是一种神经转录因子，对于中枢神经系统发育至关重要。在人类胰腺的增强子上发现了开放的染色质特征，该组织已知PAX6在胰岛素分泌中起作用。在PLCB1中，CTCFwas found to bind downstream of the enhancer and interact with PAX6, suggesting that it can probably inhibit gene activation by PAX6. PLCB4, a circadian gene that is closely located downstream of PLCB1, was identified as a candidate target gene. Hence, dysregulation of ROR1, PLCB1, or PLCB4 by PAX6 andCTCFmay be one mechanism that links neural and pancreatic dysfunction not only in insomnia but also in the relevant psychiatric disorders that are accompanied with circadian rhythm disruption and metabolic syndrome. |
| SCZ Keywords | 精神分裂症 |
| 3 | 表观遗传学2012年2月7日：155-63 |
| PMID | 22395465 |
| Title | 11p15.5上IGF2/H19印迹控制区域的表观遗传和遗传变异与小脑重量有关。 |
| Abstract | IGF2 is a paternally expressed imprinted gene with an important role in development and brain function. Allele-specific expression of IGF2 is regulated by DNA methylation at three differentially methylated regions (DMRs) spanning the IGF2/H19 domain on human 11p15.5. We have comprehensively assessed DNA methylation and genotype across the three DMRs and the H19 promoter using tissue from a unique collection of well-characterized and neuropathologically-dissected post-mortem human cerebellum samples (n = 106) and frontal cortex samples (n = 51). We show that DNA methylation, particularly in the vicinity of a keyCTCF-binding site (CTCF3）在H19上游的印迹控制区（ICR）中，与小脑重量密切相关。DNA甲基化CTCF3uniquely explains ~25% of the variance in cerebellum weight. In addition, we report that genetic variation in this ICR is strongly associated with cerebellum weight in a parental-origin specific manner, with maternally-inherited alleles associated with a 16% increase in cerebellum weight compared with paternally-inherited alleles. Given the link between structural brain abnormalities and neuropsychiatric disease, an understanding of the epigenetic and parent-of-origin specific genetic factors associated with brain morphology provides important clues about the etiology of disorders such as精神分裂症和自闭症。 |
| SCZ Keywords | 精神分裂症 |
| 4 | PLOS基因。2014年6月10日：E1004345 |
| PMID | 24901509 |
| Title | 基于综合途径的方法可以确定CTCF和CACNB2和精神分裂症的基因组区域之间的关联。 |
| Abstract | 在目前的研究中,一个集成的层次pproach was applied to: (1) identify pathways associated with susceptibility to精神分裂症; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional consequences of such single-nucleotide polymorphisms (SNPs) in the affected genes or their regulatory regions. The Global Test was applied to detect精神分裂症-associated pathways using discovery and replication datasets comprising 5,040 and 5,082 individuals of European ancestry, respectively. Information concerning functional gene-sets was retrieved from the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and the Molecular Signatures Database. Fourteen of the gene-sets or pathways identified in the discovery dataset were confirmed in the replication dataset. These include functional processes involved in transcriptional regulation and gene expression, synapse organization, cell adhesion, and apoptosis. For two genes, i.e.CTCFand CACNB2, evidence for association with精神分裂症在发现研究和发表了精神病基因组合财团的数据中，可（在基因级）可用精神分裂症study. Furthermore, these genes mapped to four of the 14 presently identified pathways. Several of the SNPs assigned toCTCF和CACNB2具有潜在的功能后果，并且与CACNB2（即ARL5B）非常接近的基因被确定为潜在的潜在基因。因此，当前分层方法的应用允许：（1）鉴定新型生物学基因组或途径，潜在参与病因精神分裂症, as well as replication of these findings in an independent cohort; (2) detection of genes of interest for future follow-up studies; and (3) the highlighting of novel genes in previously reported candidate regions for精神分裂症。 |
| SCZ Keywords | 精神分裂症 |
| 5 | 癌变2014年12月35日：2687-97 |
| PMID | 25239642 |
| Title | 通过高通量RNA测序鉴定子宫内膜癌中基因间剪接引起的嵌合TSNAX-DISC1。 |
| Abstract | 基因融合是产生新基因的主要过程之一，并被很好地描述为肿瘤发生的有效途径。在这里，通过在九个配对的人子宫内膜癌（EC）和匹配的非癌组织中进行的高通量RNA测序，我们获得了与嵌合transpin蛋白相关的因子X dimpreated In-In-中的精神分裂症1（TSNAX-DISC1）在多个EC样品中显着上调。实验研究表明，TSNAX-DISC1似乎是通过无染色体重排而形成的。嵌合体表达与CCCTC结合因子的结合成反比（CTCF）给绝缘子。随后的研究表明，较长的基因间非编码RNA lincrna-nr_034037，将TSNAX与Disc1分开，调节TSNAX -DISC1的产生和TSNAX/Disc1的表达水平CTCFfrom insulators. Dysregulation of TSNAX influences steroidogenic factor-1-stimulated transcription on the StAR promoter, altering progesterone actions, implying the association with cancer. Together, these results advance our understanding of the mechanism in which lincRNA-NR_034037 regulates TSNAX-DISC1 formation programs that tightly regulate EC development. |
| SCZ Keywords | 精神分裂症 |