遗传基因组学方法对Myoc基因调控网络的研究  

Analysis of Myocilin gene regulatory network using a genetic genomics approach

作　　者：陆宏[1] 陆璐[2] 管怀进[1] 陈辉[1] 张俊芳[1] 胡楠[1] 帅捷[1] 

机构地区：[1]南通大学附属医院眼科,226001 [2]美国田纳西大学医学中心,38163

出　　处：《中华实验眼科杂志》2013年第9期851-854,共4页Chinese Journal Of Experimental Ophthalmology

基　　金：江苏省自然科学基金项目（BK2008186）;南通市社会事业创新与示范计划项目（HS2011005）

摘　　要：背景原发性开角型青光跟（POAG）和高度近视的发病机制复杂，可能有较多致病基因及致病相关基因参与，构建基因调控网络有助于揭示发病机制。目的采用遗传基因组学方法研究Myoc基因的调控网络，探索其在POAG中的可能作用机制。方法Affymetrix基因芯片用于检测确定68个品系的BXD重组近交系（BXDRI）小鼠及其亲本C57BL／6J（B6）小鼠和DBA／2J（D2）小鼠、F1代小鼠眼组织中Myoc基因的差异表达。借助基因表达的数量性状分析（eQTL）方法，结合GeneNetwork网站（WWW．genenetwork．org）的在线分析工具，研究基因的作用特征，进而构建Myoc基因调控网络。结果Myoc基因在BXDRI小鼠眼组织中平均表达水平为10．83，不同品系小鼠表达量存在差异，其中B6小鼠表达量最高，达到11．43，BXD55小鼠表达量最低，为8．39。基因表达的eQTL分析结果显示，Myoc基因具有一个显著性QTL，其似然比统计量（LRS）达到21．78。该QTL位于2号染色体，与位于1号染色体的Myoc基因在不同的染色体，说明Myoc是反式调节基因。生物信息学分析方法进一步筛选结果提示，Olfml2a是Mroc的上游调控游候选基因。基于和Myoc高度相关基因的基因网络得以构建。结论本研究探索了Myoc的基因调控网络，显示遗传基因组学对复合性疾病发病机制的探索具有重要的指导作用。Background The pathogenesis of primary open angle glaucoma （POAG） and high myopia are very complex. To construct the regulatory network of virulence genes and relevant genes that involved in pathogenicity are helpful for reveal of the pathogenesis. Objective The aim of this study was to investigate myocilin （Myoc）, a gene that contributes to POAG and high myopia in eyes of BXD Recombinant Inbred（ BXD RI）mice and construct the regulatory network of Myoc. Methods The affymetrix microarray system was used to detect the differential expression of Myoc in the eyes of C57BL/6J （B6） , DBA/2J（D2） and BXD RI mice. Expression quantitative trait loci （eQTL） mapping was performed to construct the regulatory network of Myoc gene. Results The average expression level of the Myoc gene in the BXD strains was 10. 83 ,and the gene exhibited expression levels ranging from 8.39 in BXD55 mice tol 1.43 in B6 mice. The eQTL mapping for the Myoc gene showed a significant likelihood ratio statistic （LRS） of 21.78. The QTL was mapped in chromosome 2, and Myoc was located on chromosome 1 ,indicating that the Myoc gene was a trans-acting QTL. Olfml2a was identified to be a candidate upstream gene of Myoc by analysis of bioinformatics. Genetic regulatory network analysis demonstrated that a series of genes associated with Myoc probably played roles in the pathogenesis and development of POAG and high myopia. Conclusions The genetical genomics approach provides a powerful tool for constructing pathways that contribute to complex traits, such as POAG and high myopia.

关 键 词：基因组学 Myoc基因 网络 原发性开角型青光眼 高度近视 BXD RI小鼠 

分 类 号：R775[医药卫生—眼科]