为什么要对人类作图--人类基因组计划对人类社会的意义暨纪念人类基因组计划实施10周年

人类基因组计划 (HGP)经过 10年的实施 ,已取得巨大成果。该计划将显著改变医疗科学 ,同时也潜伏着新的危险。随着HGP的发展 ,人类社会在基因检查、药物基因组研究及基因治疗等三大应用领域有着美好的发展前景 ,同时也面临着新的困境。在将HGP成果应用于人类社会时 ,我们必须及时考虑和解决所涉及的伦理、道德和社会等问题 ,从而使HGP成果更好地为人类社会服务。     

Development of dopaminergic genetic associations with visuospatial,verbal and social working memory

Dopamine transmission in the prefrontal cortex (PFC) supports working memory (WM), the temporary holding, processing and manipulation of information in one's mind. The gene coding the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine, in particular in the PFC, has a common single nucleotide polymorphism leading to two versions of the COMT enzyme which vary in their enzymatic activity. The methionine (Met) allele has been associated with higher WM performance and lower activation of the PFC in executive function tasks than the valine (Val) allele. In a previous study, COMT genotype was associated with performance on verbal and visuospatial WM tasks in adults, as well as with performance on a novel social WM paradigm that requires participants to maintain and manipulate information about the traits of their friends or family over a delay. Here, data collected in children and adolescents (N = 202) were compared to data from the adult sample (N = 131) to investigate possible age differences in genetic associations. Our results replicate and extend previous work showing that the pattern of superior WM performance observed in Met/Met adults emerges during development. These findings are consistent with a decrease in prefrontal dopamine levels during adolescence. Developmentally moderated genetic effects were observed for both visuospatial and social WM, even when controlling for non‐social WM performance, suggesting that the maintenance and manipulation of social information may also recruit the dopamine neurotransmitter system. These findings show that development should be considered when trying to understand the impact of genetic polymorphisms on cognitive function.     

DRD4基因与亲社会行为的关联及其潜在脑机制

DRD4基因是亲社会行为的重要候选基因,且与环境交互影响亲社会行为的发生发展。通过梳理既有研究,本文从性别差异、亲社会行为的不同类型及发展动态性等角度探讨了亲社会行为遗传研究存在分歧的原因,并在此基础上探索了DRD4基因作用于亲社会行为的潜在脑机制。未来研究应采用纵向设计探究DRD4基因影响亲社会行为的发展动态性问题,并深入探索其性别差异;采用多质多法分析考察不同类型亲社会行为遗传机制的差异性;采用影像遗传学设计揭示“DRD4基因—脑—亲社会行为”作用机制。     

反社会行为的遗传基础:基因多态性和DNA甲基化

反社会行为是受遗传与环境共同影响的不良行为。分子遗传学和神经生物学的研究发现,基因以基因多态性和DNA甲基化的方式影响脑结构、功能及脑内神经递质的产生和释放,进而影响反社会行为的发生发展。本文从基因多态性和DNA甲基化两方面整理了5-HTT、MAOA、OXTR等8个候选基因与反社会行为的关联。并提出未来研究需进一步探讨基因、脑和神经递质对反社会行为的联合作用。同时,扩展多基因位点、基因多态性与DNA甲基化、积极环境与基因交互作用对反社会行为影响的研究,以全面探索反社会行为发生的遗传基础,进而更加有效的预防反社会行为。     

Association of Catechol-O-Methyltransferase Polymorphism (Val108/158Met) With Parkinson's Disease: A Meta-Analysis

Parkinson's disease (PD) is a common neurodegenerative disease, the risk factors of which are gaining more attentions. Among all these risk factors, catechol-o-methyltransferase (COMT) has been widely studied, and believed to be associated with PD. However, the relationship between COMT polymorphism and PD has not been confirmed hitherto. Therefore, a meta-analysis was performed to evaluate the effect of COMT polymorphism on PD patients. A total of 24 study subjects comprising 3,807 patients with PD and 3,942 unrelated healthy controls were recruited in this meta-analysis. Heterogeneity testing and sensitivity analysis were conducted with Review Manager 5.0 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata software (StataCorp, College Station, TX), together with publication bias by funnel plot method and modified Egger's linear regression test. No evidences of publication bias and heterogeneity were detected. In the 24 studies, the estimated odds ratios (OR) in PD patients are 0.98 for the Met allele (95% confidence interval [0.92, 1.05]) under a fixed-effects model. The authors also conducted a stratified analysis according to geographic region among Europe, Asia, and North America, the ORs for the Met allele are 0.92, 1.02, and 1.10, respectively. According to the results of the meta-analysis, a conclusion could be drawn that polymorphism of Val108/158Met are not associated with the risk of PD. However, more convincing studies are warranted to have a solid conclusion supported.     

Effects of Comt Genotype on Behavioral Symptomatology in the 22q11.2 Deletion Syndrome

The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val^158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.     

铜绿假单胞菌I类整合子及耐药基因分析

铜绿假单胞菌是临床上重要的院内感染菌,对多种抗生素耐药。整合子是能捕获并整合外源耐药基因盒,并使之表达的DNA元件。通过整合子水平转移的方式极大地加速了耐药基因在同种及不同种属之间的传播,造成细菌的耐药以至多重耐药问题日益严重。     

聊城市汉族正常人血清骨钙素参考值的研究

建立聊城市汉族正常人血清骨钙素水平的参考值。利用化学发光免疫分析法对聊城市162例汉族体检健康者血清骨钙素（BGP）水平进行检测,检测范围0．2ng／ml-100ng／ml。结果聊城市汉族正常人血清骨钙素水平的参考值为5．21±0．73ng／ml。首次报道了聊城市汉族正常人血清骨钙素参考值,为骨病骨代谢研究提供一项新的...     

COMT多态性与连续3-back任务相关ERP的关联研究

不同COMT基因型被试者,进行连续3-back任务测试,以探讨被试者工作记忆能力的变化情况。抽取21名不同COMT基因型被试者,观测被试者在连续工作记忆任务中记忆能力和脑电生理的差异。结果表明,Val/Met基因型被试者P300波幅显著低于Val/Val型,Met/Met型被试者的P300波幅居中。Val/Met型被试者显示了最差记忆任务成绩,被试者的P300波幅和记忆能力相关。COMT基因多态性和3-back任务事件相关电位相关联,工作记忆任务的灵活性和稳定性及其交互作用受到遗传因素的调控。     

Ignorance is no excuse: moral judgments are influenced by a genetic variation on the oxytocin receptor gene

Perspective-taking has become a main focus of studies on moral judgments. Recent fMRI studies have demonstrated that individual differences in brain activation predict moral decision making. In particular, pharmacological studies highlighted the crucial role for the neuropeptide oxytocin in social behavior and emotional perception. In the present study N=154 participants were genotyped for a functional polymorphism (rs2268498) in the promoter region of the OXTR gene. We found a significant difference between carriers and non-carriers of the C-allele in exculpating agents for accidental harms (F((1,152))=11.49, p=.001, η(2)=.07) indicating that carriers of the C-allele rated accidentally committed harm as significantly more blameworthy than non-carriers. This is the first study providing evidence for a genetic contribution to moral judgments.