中文摘要：

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.

英文摘要：

Objective To investigate the molecular mechanism of Alzheimer＇s disease（AD） mediated by sterol O-acyltransferase 1 （Soatl） in a whole genome level. Methods The expression variation and regulation of Soatl gene were detected by expression quantitative trait loci （eQTL） method, and eQTL of Soatl expression was determined by interval mapping in a whole genome level. The effect of single nucleotide polymorphisms between B6 and D2 mice on eQTL was then analyzecL Moreover, the trans-regulatory genes affected by Soatl in the hippocampus tissues of BXD recombinant inbred mice were selected by cluster mapping, and a genetic regulatory network of Soatl was constrcuted by Pearson correlation coefficient analysis. Results Soatl gene was a cis-eQTL. Rab2, Taz, copg, whsclll, Atrnll, 1200008A14Rik and Epdrl were the candidates for downstream genes of Soatl. The genetic regulatory network of Soatl was constructed by seventeen genes highly correlated with Soatl. Conclusion Soatl is a cis-regulatory gene. The genes in the genetic regulatory network correlate with Soatl, which is directly or indirectly involved in the pathogenesis of AD.