| 1 | Ann. N. Y. Acad. Sci. 2003 Nov 1003: 22-35 |
|---|---|
| PMID | 14684433 |
| 标题 | 基因组学和变化ionotropic glutamate receptors. |
| 抽象的 | 人，小鼠和大鼠基因组的测序使基因家族的全面信息学方法。这种方法对于鉴定基因家族的新成员，与功能保护相关的跨物种序列保护，与功能变异有关的物种多样性以及选择的历史效果相关的跨物种序列保守性是有益的。这种基因组信息学方法还将我们的注意力集中在基因位置与与表型联系的基因上。我们正在通过重新定制技术（包括贬低高性能液体染料学（DHPLC），进行筛选和直接测序）来鉴定离子型谷氨酸受体（IGR）序列变化，以及通过公众（例如DBSNP和Ensembl）和私人（即CELERA发现系统）序列数据库。在这些数据库中表示16个已知的IGR中的每一个，它们在规范物理图上的位置（例如，Celera图）建立了，并且已经进行了与小鼠和大鼠序列进行比较，从位于不同的染色体上，但在基因的同步组中发现。通过其中几种受体基因（包括Grin2b）的信息学和重新方程方法确定了38个错义变体的集合。grin3b, GRIA2, GRIA3, and GRIK1. This represents only a fraction of the sequence variation across these genes, but, in fact, these may constitute a large fraction of the common polymorphisms at these genes, and these polymorphisms are a starting point for understanding the role of these receptors in neurogenetic variation. Genetically influenced human neurobehavioral phenotypes that are likely to be linked to IGR genetic variants include addictions, anxiety/dysphoria disorders, post-brain injury behavioral disorders,schizophrenia，癫痫，疼痛感，学习和认知。因此，谷氨酸受体变异的作用可能是蛋白质，并且将变异与行为困难有关的任务。然而，（1）Catechol-O-甲基转移酶，（2）5-羟色胺转运蛋白和（3）脑衍生的神经营养因子的功能变异已与行为差异和中间表型联系起来，这表明途径在哪种途径上通过哪种途径进行了途径。IGRS可以与病因学复杂的表型相关。 |
| SCZ关键字 | schizophrenia |
| 2 | AMIA Annu Symp Proc 2011 -1 2011: 1127-33 |
| PMID | 22195173 |
| 标题 | Exploring schizophrenia drug-gene interactions through molecular network and pathway modeling. |
| 抽象的 | In this study, we retrieved 39schizophrenia-related antipsychotic drugs from the DrugBank database. These drugs had interactions with 142 targets, whose corresponding genes were defined as drug targeted genes. To explore the complexity between these drugs and their related genes inschizophrenia, we constructed a drug-target gene network. These genes were overrepresented in several pathways including: neuroactive ligand-receptor pathways, glutamate metabolism, and glycine metabolism. Through integrating the pathway information into a drug-gene network, we revealed a few bridge genes connected the sub-networks of the drug-gene network: GRIN2A,grin3b，grin2c，grin2b，drd1和drd2。这些基因编码属于NMDA受体家族和多巴胺受体的离子型谷氨酸受体。氟哌啶醇是唯一直接与这些途径和受体相互作用的药物，因此在治疗过程中可能在药物 - 基因相互作用水平上具有独特的作用schizophrenia。This study represents the first systematic investigation of drug-gene interactions in psychosis. |
| SCZ关键字 | schizophrenia |
| 3 | Transl Psychiatry 2011 -1 1: e55 |
| PMID | 22833210 |
| 标题 | Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. |
| 抽象的 | Pharmacological, genetic and expression studies implicate N-methyl-D-aspartate (NMDA) receptor hypofunction inschizophrenia(SCZ). Similarly, several lines of evidence suggest that autism spectrum disorders (ASD) could be due to an imbalance between excitatory and inhibitory neurotransmission. As part of a project aimed at exploring rare and/or de novo mutations in neurodevelopmental disorders, we have sequenced the seven genes encoding for NMDA receptor subunits (NMDARs) in a large cohort of individuals affected with SCZ or ASD (n=429 and 428, respectively), parents of these subjects and controls (n=568). Here, we identified two de novo mutations in patients with sporadic SCZ in GRIN2A and one de novo mutation in GRIN2B in a patient with ASD. Truncating mutations in GRIN2C, GRIN3A andgrin3bwere identified in both subjects and controls, but no truncating mutations were found in the GRIN1, GRIN2A, GRIN2B and GRIN2D genes, both in patients and controls, suggesting that these subunits are critical for neurodevelopment. The present results support the hypothesis that rare de novo mutations in GRIN2A or GRIN2B can be associated with cases of sporadic SCZ or ASD, just as it has recently been described for the related neurodevelopmental disease intellectual disability. The influence of genetic variants appears different, depending on NMDAR subunits. Functional compensation could occur to counteract the loss of one allele in GRIN2C and GRIN3 family genes, whereas GRIN1, GRIN2A, GRIN2B and GRIN2D appear instrumental to normal brain development and function. |
| SCZ关键字 | schizophrenia |
| 4 | 精神病学Res 2014 8月218日：356-8 |
| PMID | 24814139 |
| 标题 | A recently-discovered NMDA receptor gene, GRIN3B, is associated with duration mismatch negativity. |
| 抽象的 | The study explored associations between mismatch negativity and N-methyl-d-aspartic acid receptor subunit genes, GRIN1, GRIN2B andgrin3b在健康的受试者中schizophrenia。在138schizophreniapatients and 103 healthy subjects. Rs2240158 ofgrin3b与健康受试者的不匹配负相关性显着相关。 |
| SCZ关键字 | schizophrenia |