基于生物信息学的肝癌易感基因ARID1A低频遗传变异的功能分析

摘要

Objective To analyze the low-frequency variations in the liver cancer susceptibility gene ARID1A using a comprehensive bioinformatics strategy,and provide a clue for the genetic association studies of liver cancer.Methods 1000 Genomes Project,dbSNP,UCSC and other databases were applied to query the list of low-frequency variants.Allele frequency calculator was used to select the variants with the minor allele frequency (MAF) ≤ 5%.RegulomeDB,SNPinfo,F-SNP and other tools were utilized to predict the function of low-frequency variants.Results There were 141 and 139 variants with the MAF≤5% in the CHS and CHB data of 1000 genomes,respectively,in which 135 variants were located in the regulatory region or coding region.Nine variants had been predicted to be potential functional by RegulomeDB,SNPinfo,F-SNP and other tools.Conclusion The potentially functional variants in ARID1A with low-frequency could be used as targets in the genetic association studies of liver cancer,which may provide an evidence for exploring the effect of ARID1A low-frequency variants on the development of liver cancer.%目的 运用生物信息学方法对肝癌易感基因ARID1A的低频遗传变异进行功能初探,为后续肝癌遗传关联研究提供线索.方法 运用1000 genomes、dbSNP、UCSC等数据库检索ARID1A的低频遗传变异名录;通过RegulomeDB、SNPinfo、F-SNP等功能注释数据库预测低频变异的功能.结果 在1000 genomes的中国汉族南方人群和中国汉族北方人群数据中,ARID1A基因上MAF≤0.05的遗传变异各有141和139个,其中135个低频变异位于调控区或编码区.RegulomeDB、SNPinfo、F-SNP等数据库预测出9个潜在功能变异,分别为rs12685、rs60798877、rs6598860、rs12739212、rs139907456、rs34618114、rs191813608、rs182858322和rs78520390.结论 所识别的ARID1A基因的9个低频潜在功能变异,可作为肝癌遗传关联研究的目标变异,以助于系统阐明ARID1A低频变异对肝癌易感性的影响.