全外显子组测序筛查先天性心脏病患儿突变及功能的富集分析

Screening of mutation and functional enrichment analysis in children with congenital heart disease by whole exome sequencing

目的应用全外显子组学测序技术筛选先天性心脏病患儿基因突变位点,并分析这些位点所涉及的通路。方法提取6例均有室缺伴房缺的严重先天性心脏病患儿基因组DNA,通过全外显子组芯片捕获技术发现突变并筛选出与CHD有关的共有突变,并进一步进行功能GO富集分析。结果6例患儿中有27个SNP位点涉及17个基因,46个InDel位点涉及33个基因是符合筛选条件的共有突变,经过功能GO富集分析,SNP和InDel突变基因富集到poly(A)结合(GO:0008143)、调节心脏收缩(GO:0008016)、锌离子结合通路(GO:0008270)、机械刺激感受通路(GO:0050982)、泛素依赖的蛋白质分解代谢过程(GO:0042787)、钙离子结合通路(GO:0005509),这6条通路具有统计学意义。结论全外显子组芯片捕获技术是筛选CHD发生突变基因和功能分析的有效方法。

Objective Genetic mutation sites in children with congenital heart disease were screened by whole exome sequencing technology and the pathways involved in these sites were analyzed.Methods Genomic DNA was extracted from 6 children with congenital heart disease who all had ventricular septal defect with atrial septal defect.Mutations were detected and common mutations related to congenital heart disease were screened through the whole exome microarray capture technology,and further functional GO enrichment analysis was performed.Results Among the 6 children,27 SNP loci involved 17 genes,and 46 InDel loci involved 33 genes were common mutations that met the screening criteria.After functional GO enrichment analysis,the SNP and InDel mutant genes were enriched to poly(A)binding(GO:0008143),regulation of heart contraction(GO:0008016),zinc ion binding(GO:0008270),detection of mechanical stimulus(GO:0050982)protein ubiquitination involved in ubiquitin-dependent protein catabolic process,(GO:0042787)and calcium ion binding(GO:0005509),which showed statistical significance.Conclusion Whole exome chip capture technology is an effective method to screen mutated genes and function analysis of congenital heart disease.