Ptgs2基因在BXD重组近交系小鼠海马组织中的遗传基因组学分析

Genetic genomics analysis of Ptgs2 gene in the hippocampus of BXD recombinant inbred mice

目的研究前列腺素内过氧化物合酶(Ptgs)2基因在BXD重组近交系(RI)小鼠海马组织中的基因表达变化及表达调控。方法使用基因芯片检测BXD RI小鼠海马组织的基因表达。应用遗传基因组学研究方法进行基因表达数量性状基因座(eQTL)定位分析,寻找Ptgs2基因的上游调控位点、下游调控基因以及协同作用的基因。结果 Ptgs2基因在BXD RI小鼠海马组织中特异性高表达,且控制该基因的eQTL为顺式eQTL,该区域同时还是反式eQTL的富集区,偏相关系数分析发现其中有8个基因为Ptgs2基因的下游调控候选基因。皮尔森相关系数分析显示,BXD RI小鼠基因组中有151个基因与Ptgs2密切相关,其中前20个基因与Ptgs2的遗传相关度到达0.59以上。结论遗传基因组学研究能够有效筛选出Ptgs2基因的上游调控位点、下游调节基因及与之高度协同作用的基因,这部分基因是深入研究Ptgs2基因在多种精神类疾病中分子机制的重要靶点。

Objective To investigate the variation and regulation of prostaglandin-endoperoxide synthase（Ptgs）2 gene expression in the hippocampus of BXD recombinant inbred（RI） mice.MethodsThe gene expression in the hippocampus of BXD RI mice was analyzed by genechip.The gene expression quantitative trait locus（eQTL） was examined by genetic genomics approach to find out the potential upstream regulators,downstream targets and correlated probe sets of Ptgs2 gene.ResultsThe Ptgs2 gene was highly expressed in the hippocampus of BXD RI mice and controlled by cis-eQTL.Meanwhile,this region was also the enrich zone of trans-eQTL,in which 8 genes were suggested to be the potential downstream targets of Ptgs2 by partial correlation analysis.Pearson correlation analysis revealed that 151 probe sets were highly correlated with Ptgs2 in the BXD RI mice genomics,among which the values of the top 20 probe sets were higher than 0.59.Conclusion The genetic genomics approach effectively screens the upstream regulators,downstream targets and highly correlated probe sets of Ptgs2 gene,which could be important targets for further investigating the molecular mechanism of Ptgs2 gene in various mental diseases.