| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2009 Mar 150B: 219-25 |
|---|---|
| PMID | 18506707 |
| 标题 | Methionine sulfoxide reductase: a novel schizophrenia candidate gene. |
| 抽象的 | Methionine sulfoxide reductase (MSRA）是一种抗氧化酶，涉及氧化应激和蛋白质维持。我们以前已经报道了位于该标记D8S542的关联MSRAgene, withschizophreniain the Central Valley of Costa Rica (CVCR). By performing fine mapping analysis, we have now identified a potential three-marker at risk haplotype withinMSRA在同一CVCR样品中，全局p值略高于名义意义（p = 0.0526）。通过排序MSRA携带这种单倍型的个体中的基因，我们确定了一个新颖的4碱基对删除1,792个碱基上游。MSRA转录起始站点。这种删除的传输大大不足schizophreniapatients in the CVCR sample (P = 0.0292) using FBAT, and this was replicated in a large independent sample of 321schizophreniafamilies from the Hispanic population (P = 0.0367). These findings suggest a protective effect of the deletion againstschizophrenia。进一步，MSRAmRNA levels were significantly lower in lymphoblastoid cell lines of individuals homozygous for the deletion compared to carriers of the normal allele (P = 0.0135), although significance was only evident when genotypes were collapsed. This suggests that the deleted sequence may play a role in regulatingMSRA表达。总之，这项工作指向MSRAas a novelschizophrenia候选基因。进一步研究的机制MSRAis involved inschizophreniapathophysiology may shed light into the biological underpinnings of this disorder. |
| SCZ关键字 | schizophrenia |
| 2 | Genes Brain Behav. 2011 Oct 10: 734-9 |
| PMID | 21679298 |
| 标题 | A genome-wide association study for quantitative traits in schizophrenia in China. |
| 抽象的 | 几乎没有基因组关联研究（GWAS）schizophreniahave included Chinese populations, and verification of positive genetic findings from other ethnic groups is rare in Chinese groups. We used fluid intelligence as the quantitative trait reflectingschizophrenia在中国popula功能障碍tions, and determined the impact of genetic variation on fluid intelligence phenotypic patterns to identify genetic influences inschizophrenia。The study sample comprised 98 patients withschizophreniaand 60 healthy controls. The general fluid intelligence of participants was assessed with Cattell's Culture-Free Intelligence Test (CCFIT). Subjects were genotyped using the Illumina HumanHap 660 beadchip. We identified the methionine sulfoxide reductase A (MSRA) gene on chromosome 8 as having an association with fluid intelligence. However, only CCFIT subtest 1 (series score) demonstrated a significant result for the interaction term using the criteria of the quantitative trait (QT) analysis of 10(-5) for at least three SNPs. There were 15 haplotype blocks ofMSRAgene SNPs identified using Haploview 4.2 with solid spine D' > 0.80. The strongest QT interaction was noted in Block 3, with the most common haplotypes being AAACAGCAG and CGCAGAAGA. In conclusion, we report data from a GWAS with quantitative traits design from Chinese first-episodeschizophreniapatients and matched controls. Although the gene identified requires confirmation in an independent sample, theMSRA发现位于8号染色体上的基因与schizophrenia。 |
| SCZ关键字 | schizophrenia |
| 3 | Evol. Bioinform. Online 2013 -1 9: 29-42 |
| PMID | 23423242 |
| 标题 | A proximity-based method to identify genomic regions correlated with a continuously varying environmental variable. |
| 抽象的 | Knowledge of markers in the human genome which show spatial patterns and display extreme correlation with different environmental determinants play an important role in understanding the factors which affect the biological evolution of our species. We used the genotype data of more than half a million single nucleotide polymorphisms (SNPs) from the data set Human Genome Diversity Panel (HGDP-CEPH -CEPH) and we calculated Spearman's correlation between absolute latitude and one of the two allele frequencies of each SNP. We selected SNPs with a correlation coefficient within the upper 1% tail of the distribution. We then used a criterion of proximity between significant variants to focus on DNA regions showing a continuous signal over a portion of the genome. Based on external information and genome annotations, we demonstrated that most regions with the strongest signals also have biological relevance. We believe this proximity requirement adds an edge to our novel method compared to the existing literature, highlighting several genes (for example DTNB, DOT1L, TPCN2, RELN,MSRA, NRG3) related to body size or shape, human height, hair color, andschizophrenia。我们的方法通常可以应用于多态频率和不断变化的环境变量之间的任何关联量度。 |
| SCZ关键字 | schizophrenia |
| 4 | int。J. Neuropsychopharmacol。2014年10月17日：1707-13 |
| PMID | 24735585 |
| 标题 | Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase activity. |
| 抽象的 | 儿茶酚-O-甲基转移酶（COMT）在脑多巴胺（DA）降解中起关键作用。具体而言，较低的COMT活性导致前额叶皮层（PFC）的DA水平较高，从而减少了精神病和健康个体的注意力和认知缺陷的脆弱性。通过非同义单核苷酸多态性（SNP）显着降低了COMT活性，该多态性（SNP）通过未完全理解的后翻译后机制在残基108/158上产生缬氨酸到甲硫代替代。一种翻译后的修饰是甲二氨酸亚磺氧化物，可以通过甲硫氨酸还原酶（MSR）A和B酶降低。我们使用了重组COMT蛋白（Val/Met108）和小鼠（野生型（WT）和MSRAknockout) to determine the effect of methionine oxidation on COMT activity and COMT interaction with Msr, through a combination of enzymatic activity and Western blot assays. Recombinant COMT activity is positively regulated byMSRA, especially under oxidative conditions, whereas brains ofMSRAknockout mice exhibited lower COMT activity (as compared with their WT counterparts). These results suggest that COMT activity may be reduced by methionine oxidation, and point to Msr as a key molecular determinant for the modulation of COMT activity in the brain. The role of Msr in modulating cognitive functions in healthy individuals andschizophreniapatients is yet to be determined. |
| SCZ关键字 | schizophrenia |