| 1 | Genomics 2001 Apr 73: 123-6 |
|---|---|
| PMID | 11352574 |
| 标题 | Identification of genes from a schizophrenia-linked translocation breakpoint region. |
| Abstract | The translocation t(1:11)(q42.1,q14.3) has previously been found to be linked withschizophrenia。已经研究了1个染色体中存在的基因，但对11染色体11断点区域中的基因知之甚少。在这里，我们报告了一个BAC克隆重叠群，围绕11个断点围绕2.51 MB，该重点是使用基因组序列数据草案和该区域的现有映射数据在计算上构建的。重叠群包括26个克隆，并导致该地区10个候选基因的鉴定和相对顺序，包括2个新的转录本。它构成了多态性标记发现和关联研究的资源，以验证或拒绝候选基因。基于它们与断点及其可能的功能作用，四个候选基因似乎特别有希望。其中三个参与谷氨酸能神经传递（谷氨酸受体GRM5, NAALADase II, and a close homolog), perturbation of which is one of the most widely held theories on the underlying biochemistry ofschizophrenia。The 4th gene, tyrosinase, has been previously linked toschizophrenia通过在几种血统中使用精神病的眼皮白化病的cosogrentation。 |
| SCZ关键字 | schizophrenia, schizophrenics |
| 2 | 摩尔。精神病学2001年5月6日：311-4 |
| PMID | 11326300 |
| 标题 | The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia. |
| Abstract | The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology ofschizophreniaas they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic ofschizophrenia在另一种情况下，该基因在海马NMDA依赖性突触可塑性的调节中的一个键r。在人类中GRM5levels are increased in certain pyramidal cell neurons inschizophrenicS vs控件。（6）最后，GRM5has been mapped to 11q14, neighbouring a translocation that segregates withschizophrenia以及大型苏格兰家族中的相关精神病，F23（MLOD得分6.0）。我们确定了内含子/外显子的结构GRM5and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution betweenschizophrenics和对照（p = 0.04）。这暗示着参与GRM5基因schizophreniain this population. |
| SCZ关键字 | schizophrenia, schizophrenics |
| 3 | 摩尔。精神病学2001年5月6日：311-4 |
| PMID | 11326300 |
| 标题 | The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia. |
| Abstract | The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology ofschizophreniaas they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic ofschizophrenia在另一种情况下，该基因在海马NMDA依赖性突触可塑性的调节中的一个键r。在人类中GRM5levels are increased in certain pyramidal cell neurons inschizophrenicS vs控件。（6）最后，GRM5has been mapped to 11q14, neighbouring a translocation that segregates withschizophrenia以及大型苏格兰家族中的相关精神病，F23（MLOD得分6.0）。我们确定了内含子/外显子的结构GRM5and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution betweenschizophrenics和对照（p = 0.04）。这暗示着参与GRM5基因schizophreniain this population. |
| SCZ关键字 | schizophrenia, schizophrenics |
| 4 | J Psychiatry Neurosci 2009 Nov 34: 450-8 |
| PMID | 19949721 |
| 标题 | 人类前额叶皮质发育过程中精神分裂症易感基因的表达谱。 |
| Abstract | 人类前额叶皮层（PFC）正常发育中的破坏可能导致认知功能障碍，表现在患有schizophrenia。We sought to identify genes associated with age that are implicated inschizophrenia。 We generated genome-wide expression profiles for the PFCs of humans ranging in age from 1 month to 49 years using the Affymetrix HG-U133 plus 2.0 microarrays (54 675 transcripts). Based on the criteria of significance (false discovery rate [FDR]-adjusted q < 0.001 and r(2) > 0.6), we identified the genes associated with age in the PFC. We then performed functional annotation analyses of age-associated genes using the Gene Ontology and the Genetic Association Database (GAD). 我们发现人类PFC中基因表达的年龄依赖性变化（2281个转录本）。GAD分析表明schizophreniawas an over-represented disease class, with 42 susceptibility genes included (p < 0.001, fold enrichment = 1.66, FDR = 1.5%). Among the 42 genes, glutamate receptor genes (GRIA1, GRIK1, GRIK2, GRIN2D, GRIP1,GRM5, GRM7 and SLC1A6) were consistently downregulated across age. We confirmed microarray gene expression changes by the quantitative polymerase chain reaction experiment. 尽管许多基因在PFC发育过程中的表达发生了牢固的变化，但某些变化可能会被已知和未知因素混淆，这些因素与死后脑研究是固有的。 多schizophreniasusceptibility genes undergo age-dependent expression changes in the human PFC, and any disruption in those genes during the critical period of development may predispose the individuals toschizophrenia。 |
| SCZ关键字 | schizophrenia, schizophrenics |
| 5 | 摩尔。Psychiatry 2010 Jun 15: 637-46 |
| PMID | 19546859 |
| 标题 | Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. |
| Abstract | Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism,schizophrenia和Tourette综合征，包括A2BP1，AUTS2，CNTNAP2和IMMP2L。ADHD CNV基因集也显着富集了已知对心理和神经功能功能重要的基因，包括学习，行为，突触传播和中枢神经系统发展。四个独立的缺失位于蛋白质酪氨酸磷酸酶基因PTPRD中，最近与不安的腿综合征的候选基因有关，该基因经常呈现为ADHD。谷氨酸受体基因中的缺失，GRM5，在受影响的父母中发现，这三个受影响的后代，其ADHD表型非常相似GRM5null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD. |
| SCZ关键字 | schizophrenia, schizophrenics |
| 6 | Front Genet 2013 -1 4：58 |
| PMID | 23637704 |
| 标题 | Potential Impact of miR-137 and Its Targets in Schizophrenia. |
| Abstract | 小分子核糖核酸的重要影响di (microrna)sease pathology is becoming increasingly evident. These small non-coding RNAs have the ability to post-transcriptionally silence the expression of thousands of genes. Therefore, dysregulation of even a single miRNA could confer a large polygenic effect.schizophrenia是一种遗传上复杂的疾病，涉及多个基因，每个基因都有造成小风险。大型基因组关联研究确定了miR-137，这是一种与神经元成熟有关的miRNA，是最高风险基因之一。为了评估miR-137在该疾病中的影响的潜在影响并确定其靶标，我们使用了文献搜索，Ingenuity途径分析（IPA）和自由访问的生物信息学资源的组合。使用targetscan和schizophreniagene resource (SZGR) database, we found that in addition to CSMD1, C10orf26, CACNA1C, TCF4, and ZNF804A, fiveschizophrenia成绩单也已被验证的MiR-137目标的风险基因，还有其他schizophrenia- 可能是miR-137靶标的相关基因，包括ERBB4，GABRA1，GRIN2A，GRM5，GSK3B，NRG2和HTR2C。IPA对所有潜在目标的分析都确定了几个神经系统（NS）是包括突触长期增强的最佳规范途径，这一过程与学习和记忆机制有关，最近证明在患者中已改变schizophrenia。在NS开发和功能所涉及的目标子集中，最高的评分途径是Ephrin受体信号传导和轴突指导，对于适当的电路形成至关重要的过程，被证明在schizophrenia。These results suggest that miR-137 may indeed play a substantial role in the genetic etiology ofschizophrenia通过调节涉及神经发育和大脑功能的网络。 |
| SCZ关键字 | schizophrenia, schizophrenics |
| 7 | Gene 2013 2月515日：163-6 |
| PMID | 23149219 |
| 标题 | Evaluation of hypermethylation and expression pattern of GMR2, GMR5, GMR8, and GRIA3 in patients with schizophrenia. |
| Abstract | 新兴证据表明，谷氨酸能神经传递及其受体的功能障碍在病理生理中schizophrenia（SCZ）。这项研究评估了GMR2（谷氨酸代谢受体），GMR5，GMR8和Gria3（谷氨酸受体，离子α-Amino-Amino-Amino-3-氨基-3-羟基-5-羟基-5-甲基-4-异氧化物丙氧化物相关的启动子高甲基化和RNA表达模式）是否是否存在有风险schizophrenia之间schizophrenia患者和健康对照。 Methylation-specific polymerase chain reaction (MS-PCR) was used to estimate the promoter hypermethylation of GMR2, GMR5, GMR8, and GRIA3 genes on 81 isolated genomic DNA samples from the peripheral blood of individuals withschizophrenia和71名健康对照受试者。此外，使用实时逆转录PCR来估计34个健康对照和病例的血液样本中的mRNA水平。 The methylation of GRM2 andGRM5大大降低了schizophrenia与参考未甲基化模式[OR = 0.38，95％CI；0.144-1.035，p = 0.05;或= 0.06，95％CI;分别为0.007-0.54.10，p = 0.01]。Gria3的甲基化高度增加了schizophrenia，但不显着（OR = 2.3，95％CI； 0.51-10.42）。表达分析的结果表明，关于GRM2的相对基因表达，病例（n = 17）（n = 17）（n = 17）（n = 17）之间存在统计学上的显着差异。GRM5, and GRIA3 (p=0.0001). To the best of our knowledge, this is the first evidence showing that the promoter methylation of the GMR2 and GMR5 genes greatly decreased the risk ofschizophrenia，以及GRM2的表达水平，GRM5, and GRIA3 genes increased significantly in patients in comparison to healthy controls. These outcomes suggest that there is a need for more attention to be paid to the effect of epigenetic variations in the development of SCZ in further investigations. |
| SCZ关键字 | schizophrenia, schizophrenics |
| 8 | JAMA精神病学2013年6月70日：582-90 |
| PMID | 23553203 |
| 标题 | Support for the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia from exome sequencing in multiplex families. |
| Abstract | schizophreniais a complex genetic disorder demonstrating considerable heritability. Genetic studies have implicated many different genes and pathways, but much of the genetic liability remains unaccounted for. Investigation of genetic forms ofschizophreniawill lead to a better understanding of the underlying molecular pathways, which will then enable targeted approaches for disease prevention and treatment. To identify new genetic factors strongly predisposing toschizophrenia在有多个受影响个人的家庭中schizophrenia。 We performed genome-wide array comparative genomic hybridization, linkage analysis, and exome sequencing in multiplex families withschizophrenia。 从学术医疗中心招募了证据及其家人。 我们打算在5个大家庭中识别出罕见的引起疾病的突变schizophreniatransmission appears consistent with single-gene inheritance. Array comparative genomic hybridization was used to identify copy number variants, while exome sequencing was used to identify variants shared in all affected individuals and linkage analysis was used to further filter shared variants of interest. Analysis of select variants was performed in cultured cells to assess their functional consequences. 罕见的遗传性疾病相关基因突变。 通过阵列比较基因组杂交检测到未检测到稀有拷贝数变体。但是，在所有5个家族中，在与N-甲基-D-天冬氨酸（NMDA）受体相关的3个基因中的1个中检测到罕见的改变蛋白质的变体。一个谱系分享了错过的错过和移架的替代GRM5, encoding the metabotropic glutamate receptor subtype 5 (mGluR5), which is coupled to the NMDA receptor and potentiates its signaling; the frameshift disrupts binding to the scaffolding protein tamalin and increases mGluR5 internalization. Another pedigree transmitted a missense substitution in PPEF2, encoding a calmodulin-binding protein phosphatase, which we show influences mGluR5 levels. Three pedigrees demonstrated different missense substitutions within LRP1B, encoding a low-density lipoprotein receptor-related protein tied to both the NMDA receptor and located in a chromosome 2q22 region previously strongly linked toschizophrenia。 多重谱系的外显子组测序发现与开发风险相关的新基因schizophreniaand suggests potential novel therapeutic targets. |
| SCZ关键字 | schizophrenia, schizophrenics |
| 9 | 安。神经。2014年7月76日：82-94 |
| PMID | 24853231 |
| 标题 | Seroprevalence of autoantibodies against brain antigens in health and disease. |
| Abstract | 我们先前在健康且神经精神病患者中（n = 2,817）中报道了N-甲基-D-天冬氨酸 - 受体亚基NR1（NMDAR1）自身抗体（AB）的出乎意料的高血清阳性（约10％）（NMDAR1）自身抗体（NMDAR1）自身抗体。这一发现挑战了血清AB与脑疾病的明确因果关系。为了测试先前与病理条件相关的其他大脑抗原指导的AB获得的类似结果，我们系统地筛选了4,236个个体的血清样品。 健康的血清样本（n = 1,703）与神经精神病患者（schizophrenia, affective disorders, stroke, Parkinson disease, amyotrophic lateral sclerosis, personality disorder; total n = 2,533) were tested. For analysis based on indirect immunofluorescence, we used biochip mosaics of frozen brain sections (rat, monkey) and transfected HEK293 cells expressing respective recombinant target antigens. Seroprevalence of all screened AB was comparable in healthy and ill individuals. None of them, however, reached the abundance of NMDAR1 AB (again ~10%; immunoglobulin [Ig] G ~1%). Appreciable frequency was noted for AB against amphiphysin (2.0%), ARHGAP26 (1.3%), CASPR2 (0.9%), MOG (0.8%), GAD65 (0.5%), Ma2 (0.5%), Yo (0.4%), and Ma1 (0.4%), with titers and Ig class distribution similar among groups. All other AB were found in ?0.1% of individuals (anti-AMPAR-1/2, AQP4, CV2, Tr/DNER, DPPX-IF1, GABAR-B1/B2, GAD67, GLRA1b, GRM1,GRM5，Hu，LGL1，Recoverin，RI，ZIC4）。主要的Ig类取决于抗原位置，细胞内表位易于使用IgG（Chi-square = 218.91，p = 2.8-10（-48））。 To conclude, the brain antigen-directed AB tested here are comparably detectable in healthy subjects and the disease groups studied here, thus questioning an upfront pathological role of these serum AB. |
| SCZ关键字 | schizophrenia, schizophrenics |
| 10 | J Psychiatr Res 2014 Mar 50: 73-8 |
| PMID | 24365204 |
| 标题 | 基于蛋白质相互作用 - 基于基因组全基因组关联分析的精神分裂症分析。 |
| Abstract | schizophrenia是一种严重的神经精神疾病，具有强大而复杂的遗传背景。最近全基因组关联研究（GWAS）成功地确定了几个敏感性基因座schizophrenia。为了解释遗传变异的功能作用，并检测其中一些基因对schizophrenia, protein-interaction-network-based analysis (PINBA) has emerged as an effective approach. In the current study, we conducted a PINBA of our previous GWAS data taken from the Han Chinese population. In order to do so, we used dense module search (DMS), a method that locates densely connected modules for complex diseases by integrating the association signal from GWAS datasets into the human protein-protein interaction (PPI) network. As a result, we identified one gene set with a joint effect significantly associated withschizophreniaand gene expression profiling analysis suggested that they were mainly neuro- and immune-related genes, such as glutamatergic gene (GRM5），GABA能基因（GABRB1，GABARAP）和位于MHC区域（HLA-C，TAP2，HIST1H1B）的基因。进一步的途径富集分析表明，这些基因参与与神经元和免疫系统有关的过程，例如粘附连接途径，神经营养蛋白信号通路和Toll类受体信号通路。在我们的研究中，我们确定了一组在单标记GWAS中遗漏的敏感性基因，我们的发现可以促进对遗传机制的研究schizophrenia。 |
| SCZ关键字 | schizophrenia, schizophrenics |
| 11 | 神经药理学2015年9月1日：-1 |
| PMID | 26349010 |
| 标题 | 转向精神分裂症中MGLUR5失调模型：对未来精神分裂症治疗的后果。 |
| Abstract | Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by theGRM5fo基因,代表了一种引人注目的新型药物目标r the treatment ofschizophrenia。mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted inschizophrenia。因此，MGLUR5阳性变构调节剂在临床前表现出令人鼓舞的治疗潜力schizophrenia模型，特别是用于治疗当前可用治疗剂的认知功能障碍。需要更多的工作来支持MGLUR5靶向药物的进展到诊所schizophreniatreatment, although some obstacles may be overcome by comprehensively understanding how mGluR5 itself is involved in the neurobiology of the disorder. Several processes that are necessary for the regulation of mGluR5 activity have been identified, but not examined, in the context ofschizophrenia。These processes include protein-protein interactions, dimerisation, subcellular trafficking, the impact of genetic variability or mutations on protein function, as well as epigenetic, post-transcriptional and post-translational processes. It is essential to understand these aspects of mGluR5 to determine whether they are affected inschizophreniapathology, and to assess the consequences of mGluR5 dysfunction for the future use of mGluR5-based drugs. Here, we summarise the known processes that regulate mGluR5 and those that have already been studied inschizophrenia, and discuss the consequences of this dysregulation for current mGluR5 pharmacological strategies. |
| SCZ关键字 | schizophrenia, schizophrenics |