| 1 | Schizophr. Res. 2004 Mar 67: 41-52 |
|---|---|
| PMID | 14741323 |
| Title | Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. |
| Abstract | In order to help prioritize the selection of candidate genes and to study possible trait and not state related changes in gene expression, we compared lymphocytic gene expression patterns of five individual family members withschizophreniaand nine unaffected individuals from a large multiplex high density pedigree. We screened gene expression by microarray consisting of 1128 brain focused genes. Three criteria for selection of microarray gene differences betweenschizophreniaand unaffected family members were employed: a significant t-test, expression in a majority of subjects, and fold change magnitude. Gene expression levels were significantly different for nine genes between individuals withschizophreniacompared to unaffected controls, and two genes were validated by real-time PCR. The expression of the neuropeptide Y receptor Y1 gene (NPY1Rlocalized at 4q31.3-q32) and the human guanine nucleotide-binding regulatory protein Go-alpha (GNAO1 localized at 16q13) was significantly decreased in individuals withschizophreniacompared to unaffected family controls by microarray and real-time PCR. The cytosolic malate dehydrogenase gene (MDH1 localized at 2p13.3) was also significantly increased by microarray analysis and showed a trend for increase by real-time PCR. The significant genes are discussed in terms of proximity to linkage regions, prior association studies ofschizophrenia, and other reports of microarray screening ofschizophreniatissue. Evidence from these studies taken together with the present study suggests critical pathways inschizophreniamay be studied in peripheral tissue as part of the strategy in functional genomic convergence. This preliminary study needs to be repeated by screening a larger set of genes in additional families withschizophrenia。The present study offers support for examination of gene expression patterns using lymphocytic RNA for complex neuropsychiatric disorders from large cohorts of patients. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | J. Hum. Genet. 2011 Jul 56: 478-83 |
| PMID | 21512575 |
| Title | Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia. |
| Abstract | The dysbindin-1 and neuregulin-1 (NRG-1) genes are related toschizophrenia。Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects withschizophrenia。除了采样的困难,se of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes inschizophreniahave been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R和GNAO1）在来自45例患者的永生淋巴细胞中schizophreniaand 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1,NPY1R或GNAO1基因。我们的发现表明，来自永生的淋巴细胞的基因表达谱。schizophrenicpatients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | J. Hum. Genet. 2011 Jul 56: 478-83 |
| PMID | 21512575 |
| Title | Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia. |
| Abstract | The dysbindin-1 and neuregulin-1 (NRG-1) genes are related toschizophrenia。Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects withschizophrenia。除了采样的困难,se of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes inschizophreniahave been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R和GNAO1）在来自45例患者的永生淋巴细胞中schizophreniaand 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1,NPY1R或GNAO1基因。我们的发现表明，来自永生的淋巴细胞的基因表达谱。schizophrenicpatients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Front Behav Neurosci 2014 -1 8: 388 |
| PMID | 25414651 |
| Title | Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens. |
| Abstract | 孕产涉及自然奖励的转变，从而使后代变得高度收获。伏隔核（NAC）是自然奖励和成瘾的关键中枢神经系统区域，但迄今为止，尚无大规模评估NAC中的事件，这是自然奖励的母亲变化的基础。在这项研究中，我们利用微阵列和生物信息学方法来评估小鼠产后NAC基因表达变化。模块化的单集富集测试（MSET）表明，在五个独立策划的数据库中的五个（例如，malacards，phenopedia）中的五个中的五个中，与成瘾和奖励有关的基因和奖励相关的基因和奖励相关的基因和奖励显着富集了产后（相对于Virgin）NAC基因表达谱。确定了100多种成瘾/奖励相关的基因，其中包括：PER1，PER2，ARC，HOMER2，CREB1，GRM3，FOSB，GABRB3，ADRA2A，NTRK2，CRY1，PENK，PENK，CARTPT，CARTPT，ADCY1，1NPY1R, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), andschizophrenia。Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. |
| SCZ关键字 | 精神分裂症，精神分裂症 |