【摘要】 目的从全基因组水平研究甾醇氧-酰基转移酶1(Soat1)介导的阿尔兹海默病(AD)发病的分子机制。方法运用基因表达数量性状基因座(eQTL)定位方法对Soat1基因的表达变异及表达调控进行研究,采用区间作图在全基因组水平定位控制Soat1基因表达变化的eQTL。分析B6小鼠和D2小鼠两品系间的单核苷酸多态性对eQTL定位的影响。采用聚类分析筛选BXD重组近交系小鼠海马组织基因组中受Soat1基因反式调节的候选基因,通过Pearson相关系数法构建Soat1基因的表达遗传调控网络。结果Soat1基因为顺式作用的eQTL,Rab2、Taz、copg、whsc1l1、Atrnl1、1200008A14Rik和Epdr1为该基因的下游候选调控基因。与Soat1基因高度相关的前17个基因构建遗传相关基因网络。结论 Soat1基因为顺式调控基因;遗传相关基因网络中的基因与Soat1基因存在相互作用,直接或间接参与了AD的发病。更多还原

【Abstract】 Objective To investigate the molecular mechanism of Alzheimer′s disease(AD) mediated by sterol O-acyltransferase 1(Soat1)in a whole genome level.Methods The expression variation and regulation of Soat1gene were detected by expression quantitative trait loci(eQTL) method,and eQTL of Soat1expression was determined by interval mapping in a whole genome level. The effect of single nucleotide polymorphisms between B6and D2mice on eQTL was then analyzed. Moreover,the trans-regulatory genes affected by Soat1 in the hippocampus tissues of BXD recombinant inbred mice were selected by cluster mapping,and a genetic regulatory network of Soat1 was constrcuted by Pearson correlation coefficient analysis.Results Soatl gene was a cis-eQTL. Rab2,Taz,copg,whsc1l1,Atrnl1,1200008A14Rik and Epdr1 were the candidates for downstream genes of Soat1.The genetic regulatory network of Soat1was constructed by seventeen genes highly correlated with Soat1.Conclusion Soatl is a cis-regulatory gene.The genes in the genetic regulatory network correlate with Soat1,which is directly or indirectly involved in the pathogenesis of AD.更多还原