| 1 | Neurosci. Lett. 2009 Nov 465: 248-51 |
|---|---|
| PMID | 19766700 |
| Title | Association and expression study of synapsin III and schizophrenia. |
| Abstract | synapsin III创e,SYN3, which belongs to the family of synaptic vesicle-associated proteins, has been implicated in the modulation of neurotransmitter release and in synaptogenesis, suggesting a potential role in several neuropsychiatric diseases. The humanSYN3gene is located on chromosome 22q12-13, a candidate region implicated in previous linkage studies ofschizophrenia. However, association studies ofSYN3andschizophreniahave produced inconsistent results. In this study, fourSYN3SNPs (rs133945 (-631 C>G), rs133946 (-196 G>A), rs9862 and rs1056484) were tested in three sets of totally 3759 samples that comprise 655 affected subjects and 626 controls in the Irish Case-Control Study ofschizophrenia（ICCSS），1350个样品，在爱尔兰的高密度研究中掺入273个血统schizophreniaFamilies (ISHDSF), and 564 unrelatedschizophrenia中国病例对照样本中的患者和564个健康个体。表达水平SYN3inschizophrenicpatients and unaffected controls were compared using postmortem brain cDNAs provided by the Stanley Medical Research Institute (SMRI). There was no significant association in either the Irish or Chinese case-control samples, nor in the combined samples. Consistent with this finding, we did not find any significant difference in allele or haplotype frequencies when we used the pedigree disequilibrium test to analyze the Irish family sample. In the expression studies, no significant difference (p=0.507) was observed between patients and controls. Both the association studies and expression studies didn't support a major role forSYN3in the susceptibility ofschizophrenia在爱尔兰和中国人口中。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | Neurosci. Lett. 2009 Nov 465: 248-51 |
| PMID | 19766700 |
| Title | Association and expression study of synapsin III and schizophrenia. |
| Abstract | synapsin III创e,SYN3, which belongs to the family of synaptic vesicle-associated proteins, has been implicated in the modulation of neurotransmitter release and in synaptogenesis, suggesting a potential role in several neuropsychiatric diseases. The humanSYN3gene is located on chromosome 22q12-13, a candidate region implicated in previous linkage studies ofschizophrenia. However, association studies ofSYN3andschizophreniahave produced inconsistent results. In this study, fourSYN3SNPs (rs133945 (-631 C>G), rs133946 (-196 G>A), rs9862 and rs1056484) were tested in three sets of totally 3759 samples that comprise 655 affected subjects and 626 controls in the Irish Case-Control Study ofschizophrenia（ICCSS），1350个样品，在爱尔兰的高密度研究中掺入273个血统schizophreniaFamilies (ISHDSF), and 564 unrelatedschizophrenia中国病例对照样本中的患者和564个健康个体。表达水平SYN3inschizophrenicpatients and unaffected controls were compared using postmortem brain cDNAs provided by the Stanley Medical Research Institute (SMRI). There was no significant association in either the Irish or Chinese case-control samples, nor in the combined samples. Consistent with this finding, we did not find any significant difference in allele or haplotype frequencies when we used the pedigree disequilibrium test to analyze the Irish family sample. In the expression studies, no significant difference (p=0.507) was observed between patients and controls. Both the association studies and expression studies didn't support a major role forSYN3in the susceptibility ofschizophrenia在爱尔兰和中国人口中。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | Biol. Psychiatry 2011 Jun 69: 1109-16 |
| PMID | 21392734 |
| Title | Genetic dissection of behavioral flexibility: reversal learning in mice. |
| Abstract | Behavioral inflexibility is a feature ofschizophrenia，注意力缺陷/多动障碍和行为成瘾可能是由于对行为的抑制性控制的遗传缺陷而导致的。在这里，我们研究了使用操作逆转学习任务测量灵活性个体差异的遗传基础。 We quantified discrimination acquisition and subsequent reversal learning in a cohort of 51 BXD strains of mice (2-5 mice/strain, n = 176) for which we have matched data on sequence, gene expression in key central nervous system regions, and neuroreceptor levels. Strain variation in trials to criterion on acquisition and reversal was high, with moderate heritability (?.3). Acquisition and reversal learning phenotypes did not covary at the strain level, suggesting that these traits are effectively under independent genetic control. Reversal performance did covary with dopamine D2 receptor levels in the ventral midbrain, consistent with a similar observed relationship between impulsivity and D2 receptors in humans. Reversal, but not acquisition, is linked to a locus on mouse chromosome 10 with a peak likelihood ratio statistic at 86.2 megabase (p < .05 genome-wide). Variance in messenger RNA levels of select transcripts expressed in neocortex, hippocampus, and striatum correlated with the reversal learning phenotype, includingSYN3, Nt5dc3, and Hcfc2. This work demonstrates the clear trait independence between, and genetic control of, discrimination acquisition and reversal and illustrates how globally coherent data sets for a single panel of highly related strains can be interrogated and integrated to uncover genetic sources and molecular and neuropharmacological candidates of complex behavioral traits relevant to human psychopathology. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Int. J. Neuropsychopharmacol. 2013 Mar 16: 289-99 |
| PMID | 22571925 |
| Title | H3K4 tri-methylation in synapsin genes leads to different expression patterns in bipolar disorder and major depression. |
| Abstract | The synapsin family of neuronal phosphoproteins is composed of three genes (SYN1, SYN2 andSYN3) with alternative splicing resulting in a number of variants with various levels of homology. These genes have been postulated to play significant roles in several neuropsychiatric disorders, including bipolar disorder,schizophreniaand epilepsy. Epigenetic regulatory mechanisms, such as histone modifications in gene regulatory regions, have also been proposed to play a role in a number of psychiatric disorders, including bipolar disorder and major depressive disorder. One of the best characterized histone modifications is histone 3 lysine 4 tri-methylation (H3K4me3), an epigenetic mark shown to be highly enriched at transcriptional start sites and associated with active transcription. In the present study we have quantified the expression of transcript variants of the three synapsin genes and investigated their relationship to H3K4me3 promoter enrichment in post-mortem brain samples. We found that histone modification marks were significantly increased in bipolar disorder and major depression and this effect was correlated with significant increases in gene expression. Our findings suggest that synapsin dysregulation in mood disorders is mediated in part by epigenetic regulatory mechanisms. |
| SCZ关键字 | 精神分裂症，精神分裂症 |