再生障碍性贫血患者外周血全外显子组高通量基因测序分析
High throughput gene sequencing analysis of peripheral blood whole exomes in patients with aplastic anemia
王金鑫 1李昌年 2王腾 2魏文健 2史镜铂 2王琰 1徐瑞荣 1崔思远1
作者信息
- 1. 山东中医药大学附属医院,山东 济南 250014
- 2. 山东中医药大学,山东 济南 250355
- 折叠
摘要
目的:对再生障碍性贫血(再障)患者进行外周血全外显子测序,观察基因突变的类型及突变率以探讨再障的发病机制.方法:采集19例再障患者的外周血并提取单个核细胞进行全外显子测序,对所得基因进行GO和KEGG富集分析.数据采用SPSS 22.0进行统计分析,以P<0.05为存在显著差异.结果:测得19例再障患者共有2006个基因突变,参照GeneCards及OMIM数据库及患者测序结果筛选出49个基因,绘制患者基因突变图谱,发现MUC5B基因可能与再障发病相关,其突变率达100%,其余基因如ERCC6、SYNE1和WFS1等突变率均超过40%,亦可能参与再障的形成.在GO分析中其主要与细胞运动、细胞骨架及组成、蛋白结合等功能相关.KEGG通路分析中,主要是在Hippo通路、ECM-受体相互作用通路等地方富集.结论:MUC5B基因可能是造成T细胞比例失调,进而导致再障的关键基因.此外,Hippo通路可能通过调节T细胞比例、端粒酶活性等参与再障的发病机制.
Abstract
AIM:The whole exome from the peripheral blood of 19 patients with aplastic anemia was se-quenced,and the type and rate of gene mutation were observed to explore the pathogenesis of aplastic anemia.METH-ODS:Peripheral blood samples from 19 patients with aplastic anemia were collected,and mononuclear cells were extract-ed for whole exome sequencing.Enrichment analyses of the obtained genes were conducted using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).Data were statistically analyzed using IBM SPSS version 22.0,and P<0.05 indicated statistically significant differences.RESULTS:Overall,2006 gene mutations were identified in 19 patients with aplastic anemia,and 49 genes were selected based on GeneCards and OMIM databases and sequencing re-sults.A gene mutation map of the patient was drawn,which revealed a potential association of MUC5B gene with the onset of aplastic anemia,with a mutation rate of 100%.Other genes,such as ERCC6,SYNE1 and WFS1,have mutation rates exceeding 40%and may be involved in the development of aplastic anemia.In GO analysis,it was mainly related to cell movement,cytoskeleton composition,protein binding,and other functions.In the KEGG pathway analysis,the Hippo pathway and the extracellular matrix-receptor interaction pathway were the main enrichment areas.CONCLUSION:MUC5B may be a key gene that causes T cell imbalance,leading to aplastic anemia.The Hippo pathway may also partici-pate in the pathogenesis of aplastic anemia through regulatory T cells and telomerase activity.
关键词
再生障碍性贫血/外显子测序/基因突变/Hippo信号通路Key words
aplastic anemia/exome sequencing/gene mutation/Hippo signaling pathway引用本文复制引用
基金项目
国家自然科学基金(82174181)
山东省自然科学基金(ZR2020KH023)
山东省医药卫生科技发展计划(202003040045)
山东省医药卫生科技发展计划(2018WS184)
出版年
2024
国家科技期刊平台
NSTL
维普
万方数据