LRRK2基因G2019S突变帕金森病相关基因的生物信息学分析  

Bioinformatics analysis of genes related to Parkinson's disease with LRRK2( G2019S) mutation

作　　者：陈光乐[1] 郑文岭[1] 马文丽[1] 

机构地区：[1]南方医科大学基因工程研究所,广州510515

出　　处：《解剖学报》2015年第3期304-309,共6页Acta Anatomica Sinica

基　　金：国家自然科学基金资助项目(39880032);广东省领军人才基金资助项目(C1030925)

摘　　要：目的从分子水平揭示富亮氨酸重复激酶2(LRRK2)基因G2019S突变帕金森病的发病机制,为临床诊断及治疗提供新思路。方法在公共基因芯片数据库(GEO)中下载LRRK2基因G2019S突变帕金森病的相关基因芯片数据(GSE22491),其中LRRK2(G2019S)突变帕金森病样本10例,正常控制组样本8例,利用Qlucore Omics Explorer(QOE)3.0软件、DAVID、STRING等在线分析软件对LRRK2基因G2019S突变帕金森病差异基因进行生物信息学分析。结果 QOE3.0分析筛选出1752个LRRK2基因G2019S突变帕金森病差异基因,其中上调191个,下调1561个。对其进行生物信息学分析发现,SKP2、RBX1、SKP1、CUL1、CUL4A等基因以及核糖体信号通路、氧化磷酸化信号通路、蛋白酶体信号通路、白细胞跨内皮迁移信号通路、磷酸戊糖途径信号通路、枸橼酸信号通路、Fcγ受体(FcγR)介导的吞噬通路等在LRRK2基因G2019S突变帕金森病的发生发展中可能起着重要作用。结论通过生物信息学分析LRRK2基因G2019S突变帕金森病相关基因芯片数据,提示LRRK2基因G2019S突变帕金森病发病是多种基因、多种分子机制相互作用的结果,对相关分子机制的进一步分析有利于揭示LRRK2基因G2019S突变帕金森病的发病机制。Objective To investigate the genes from Parkinson＇ s disease （PD） patients carrying the mutation of leucine-rich repeat kinase 2 （LRRK2） gene（G2019S） and to explore the molecular mechanism of Parkinson＇ s disease. Methods Microarray dataset GSE22491 from the Gene Expression Omnibus database, the dataset includes 10 PD and 8 control samples, and analyzed by bioinformatics methods using Qlucore Orates Explorer （QOE）3.0, DAVID and String. Results A total of 1752 genes were identified as differentially expressed genes, of which 191 were up-regulated and 1561 were down-regulated in PD. The main biological pathways involved included ribosome, oxidative phosphorylation, proteasome, leukocyte transendothelial migration,pentose phosphate pathway, citrate cycle, Fc gamma receptor-mediated phagocytosis and genes of SKP2, RBX1, SKP1, CULl, CUIAA, etc. They might play important roles in the molecular mechanism of Parkinson＇ s disease. Conclusion The pathogenesis of PD involves multiple genes, and investigations of these genes may provide valuable insights into the mechanism of PD with mutation of LRRK2 gene （G2019）.

关 键 词：富亮氨酸重复激酶2 帕金森病 基因芯片 生物信息学 人 

分 类 号：R741.02[医药卫生—神经病学与精神病学]