| 1 | Proc. Natl. Acad. Sci. U.S.A. 2006 May 103: 7729-34 |
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| PMID | 16684884 |
| 标题 | TBX1单倍症与小鼠和人类的行为障碍有关：对22Q11缺失综合征的影响。 |
| 抽象的 | About 35% of patients with 22q11 deletion syndrome (22q11DS), which includes DiGeorge and velocardiofacial syndromes, develops psychiatric disorders, mainly精神分裂症和躁郁症。We previously reported that mice carrying a multigene deletion (Df1) that models 22q11DS have reduced prepulse inhibition (PPI), a behavioral abnormality and精神分裂症内型。Impaired PPI is associated with several psychiatric disorders, including those that occur in 22q11DS, and recently, reduced PPI was reported in children with 22q11DS. Here, we have mapped PPI deficits in a panel of mouse mutants that carry deletions that partially overlap with Df1 and have defined a PPI critical region encompassing four genes. We then used single-gene mutants to identify the causative genes. We show that PPI deficits in Df1/+ mice are caused by haploinsufficiency of two genes, Tbx1 andGNB1L。Mutation of either gene is sufficient to cause reduced PPI. Tbx1 is a transcription factor, the mutation of which is sufficient to cause most of the physical features of 22q11DS, but the gene had not been previously associated with the behavioral/psychiatric phenotype. A likely role for Tbx1 haploinsufficiency in psychiatric disease is further suggested by the identification of a family in which the phenotypic features of 22q11DS, including psychiatric disorders, segregate with an inactivating mutation of TBX1. One family member has Asperger syndrome, an autistic spectrum disorder that is associated with reduced PPI. Thus, Tbx1 andGNB1Lare strong candidates for psychiatric disease in 22q11DS patients and candidate susceptibility genes for psychiatric disease in the wider population. |
| SCZ关键字 | 精神分裂症 |
| 2 | Dev Disabil Res Rev 2008 -1 14：26-34 |
| PMID | 18636634 |
| 标题 | 候选基因和22Q11.2缺失综合征中的行为表型。 |
| 抽象的 | 有一个压倒性的证据表明，患有22q11.2缺失综合征（22q11.2ds）的儿童和成人具有特征性的行为表型。特别是，越来越多的证据表明22q11.2ds和精神分裂症, especially in adulthood. Deletion of 22q11.2 is the third highest risk for the development of精神分裂症，只有两个父母的孩子，只有更大的风险精神分裂症或受影响个体的单卵双重二线。与人的联系和协会研究精神分裂症have implicated several susceptibility genes, of which three are in the 22q11.2 region; catechol-o-methyltransferase (COMT), proline dehydrogenase (PRODH), andGNB1L。另外，变化GNB1L与22q11.2ds男性的精神病的存在有关。在22q11.2d的鼠标模型中，TBX1和GNB1L与减少的预硫抑制作用有关精神分裂症内型。22q11.2ds的研究提供了一个有吸引力的模型，以增加我们对精神分裂症以及22q11.2ds和更广泛的人群中的其他精神疾病。 |
| SCZ关键字 | 精神分裂症 |
| 3 | 嗡嗡声。摩尔,麝猫。2008年2月17日:555 - 66 |
| PMID | 18003636 |
| 标题 | Strong evidence that GNB1L is associated with schizophrenia. |
| 抽象的 | Evidence that a gene or genes on chromosome 22 is involved in susceptibility to精神分裂症comes from two sources: the increased incidence of精神分裂症在患有22q11缺失综合征（22q11ds）和遗传连锁研究的个体中。在小鼠中，tbx1或GNB1Lcan cause deficits in pre-pulse inhibition, a sensory motor gating defect which is associated with精神分裂症。We tested the hypothesis that variation at this locus confers risk of精神分裂症and related disorders in a series of case-control association studies. First, we found evidence for a male-specific genotypic association (P = 0.00017) TBX1/GNB1L在662精神分裂症cases and 1416 controls from the UK. Moreover, we replicated this finding in two independent case-control samples (additional 746 cases and 1330 controls) (meta analysis P = 1.8 x 10(-5)) and also observed significant evidence for genotypic association in an independent sample of 480精神分裂症来自保加利亚的父型三重奏在该基因座处有标记，这在男性概率中又是最强的（p = 0.004）。在具有和没有精神病的22q11ds的83名受试者样本中，基因分型再次显示出与22q11ds的男性精神病有显着的等位基因关联（p = 0.01）。最后，使用特定于等位基因的表达分析，我们表明与精神病相关的标记也与变化有关GNB1Lexpression, raising the hypothesis that the risk to develop psychosis at this locus could be mediated in a dose sensitive manner via gene expression. However, other explanations are possible, and further analyses will be required to clarify the correct functional mechanism. |
| SCZ关键字 | 精神分裂症 |
| 4 | Schizophr Bull 2010年7月36日：756-65 |
| PMID | 19011233 |
| 标题 | Supportive evidence for reduced expression of GNB1L in schizophrenia. |
| 抽象的 | Chromosome 22q11 deletion syndrome (22q11DS) increases the risk of development of精神分裂症与一般人群相比，超过10倍以上，表明22q11ds区域中包含的20个以上基因的子集的单倍不足可能会增加精神分裂症。在本研究中，我们筛选了位于22q11ds区域的基因精神分裂症than in those of controls. 通过Illumina Human-6表达珠芯片阵列筛选基因表达，并通过实时逆转录 - 聚合酶链反应测定和蛋白质印迹分析确认。 Expression ofGNB1Lwas lower in patients with精神分裂症比澳大利亚人的对照对象（10精神分裂症cases and 10 controls) and Japanese (43精神分裂症病例和11个对照）大脑样本。由于其表达水平低，无法评估TBX1。其他基因的表达水平在患者中没有显着降低精神分裂症than in control subjects. Association analysis of tag single-nucleotide polymorphisms in theGNB1L基因区域没有证实1918年日本的过量纯合性精神分裂症案例和1909年日本控件。氟哌啶醇治疗增加了50周GNB1L小鼠前额叶皮层中的基因表达。 Taken together with the impaired prepulse inhibition observed in heterozygousGNB1L上一项研究报告的敲除小鼠，目前的发现支持断言GNB1L是22q11ds地区的基因之一，负责增加精神分裂症。 |
| SCZ关键字 | 精神分裂症 |
| 5 | 精神病学水库2011年5月187日：457-9 |
| PMID | 20538345 |
| 标题 | 中国汉族人群中GNB1L和三个主要精神障碍的协会研究。 |
| 抽象的 | 我们在GNB1L和三种精神障碍（重度抑郁症，躁郁症，精神分裂症）中国人口。在1135例案件和1135个对照中，调查结果表明GNB1L与躁郁症和精神分裂症而不是严重的抑郁症。 |
| SCZ关键字 | 精神分裂症 |
| 6 | PLoS ONE 2012 -1 7: e33473 |
| PMID | 22457764 |
| 标题 | 功能性基因表达分析显示，与精神分裂症相关的途径在22q11缺失综合征患者中受到参与。 |
| 抽象的 | 22Q11缺失综合征（22q11ds）与畸形学和高患病率有关精神分裂症-like symptoms. Several genes located on chromosome 22q11 have been linked to精神分裂症。删除被认为破坏了与神经元和神经元电路的成熟和发展以及神经递质的成熟和发育有关的表达。我们研究了822q11ds患者和8个年龄和性别匹配的对照的外周血单核细胞（PBMC）的全基因组基因表达，以研究22q11基因的表达水平和（2）研究22q11基因是否参与在功能性遗传网络中与精神分裂症。使用Ingenuity Pathways分析（IPA）研究了在患者中差异表达的基因之间的功能关系（通过局部适应性统计程序（LAP）或满足P <0.05和倍数变化> 1.5）。14个样本（7例，7个对照）通过了质量控制。LAP鉴定出29个放松管制的基因。途径分析显示，患者和对照组之间有262次转录本差异表达。功能途径最受欢迎的是细胞死亡，细胞形态，细胞组装和组织以及细胞对细胞信号传导。此外，还确定了10条规范途径，其中自然杀伤细胞的信号途径，神经营养蛋白/TRK，Neuregulin，轴突引导和亨廷顿氏病。我们的发现支持将22q11ds用作研究模型beplay苹果手机能用吗精神分裂症。我们确定了几个基因的表达降低（其中包括COMT，UFD1L，PCQAP和GNB1L）以前链接到精神分裂症以及与精神分裂症, of which Neurotrophin/Trk and neuregulin signaling seems to be especially notable. |
| SCZ关键字 | 精神分裂症 |
| 7 | 是。J. Med。基因。B Neuropsychiatr。基因。2012年1月159b：61-71 |
| PMID | 22095694 |
| 标题 | GNB1L参与自闭症的证据。 |
| 抽象的 | 染色体22q11.2的结构变化由非平行性同源重组介导的区域22q11.2缺失（DEL22Q11.2）和22q11.2重复（DUP22Q11.2）综合征。大多数DEL22Q11.2病例都有面部和心脏畸形，免疫障碍，特定的认知概况以及增加的风险精神分裂症和自闭症谱系障碍（ASDS）。DUP22Q11.2的表型通常没有物理特征，但包括神经认知异常的谱。尽管有充分的证据表明，TBX1的单倍不使人不足在DEL22Q11.2的物理特征中起作用，但尚不清楚关键1.5？MB区域中哪个基因是造成观察到的行为表型频谱的原因。我们确定了一个平衡易位46，xy，t（1; 22）（p36.1; q11.2）的人，以及以认知障碍，自闭症和自闭症和特征的行为表型精神分裂症在没有先天性畸形的情况下。使用体细胞杂交和比较基因组杂交（CGH），我们映射了染色体22的断点，内含子7中的内含子7GNB1L基因。拷贝数评估和直接DNA测序GNB1Lin 271精神分裂症and 513 autism cases revealed dup22q11.2 in two families with autism and privateGNB1Lmissense variants in conserved residues in three families (P?=?0.036). The identified missense variants affect residues in the WD40 repeat domains and are predicted to have deleterious effects on the protein. Prior studies provided evidence thatGNB1L可能在精神分裂症。我们的发现支持参与GNB1L在ASD中也是如此。 |
| SCZ关键字 | 精神分裂症 |
| 8 | Neurosci Bull 2015 2月31日：43-52 |
| PMID | 24831436 |
| 标题 | The schizophrenia/bipolar disorder candidate gene GNB1L is regulated in human temporal cortex by a cis-acting element located within the 3'-region. |
| 抽象的 | 22q11.2缺失综合征（DS）是一种复杂的发育障碍，具有高精神病的发病率，包括精神分裂症和情绪障碍。最近的研究已经确定了鸟嘌呤核苷酸结合蛋白（G蛋白）β多肽1类（GNB1L), located within the 1.5 Mbp 22q11.2 DS critical region, as a candidate liability gene for精神分裂症和躁郁症。在这项研究中，我们使用了汉族中国颞颞皮层和连锁不平衡（LD）分析中的mRNA表达测量结果表明GNB1Lis regulated by a cis-acting genetic variant within the 3'-region of the gene. Significantly, this variant is located within an LD block that contains all of the common SNPs previously shown to associate with精神分裂症and bipolar disorder in Han Chinese and Caucasian populations. Contrary to our expectations, re-analysis of previously published case-control study data in light of our mRNA expression results implies that theGNB1L高表达等位基因是风险等位基因精神分裂症和汉族人口中的躁郁症。 |
| SCZ关键字 | 精神分裂症 |