Identification of rare variants in novel candidate genes in pulmonary atresia patients by next generation sequencing
| Autor: | Huilin Xie, Xin Shi, Ruilin Zhang, Tieliu Shi, Qihua Fu, Kai Bai, Kun Sun, Yanan Lu, Sun Chen, Yu Yu, Li Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Candidate gene
ACMG American College of Medical Genetics Gene mutation Pulmonary atresia Biochemistry Pathogenesis 0302 clinical medicine ExAC Exome Aggregation Consortium GSEA gene set enrichment analysis Structural Biology RT-qPCR Reverse Transcription Quantitative PCR Medicine GEO Gene Expression Omnibus TOF tetralogy of Fallot gnomAD Genome Aggregation Database Exome sequencing LOF loss-of-function Genetics 0303 health sciences Congenital heart defect PA Pulmonary atresia SNP single nucleotide polymorphism CHD congenital heart defect HPAECs Human Pulmonary Artery Endothelial Cells Computer Science Applications RV right ventricle Whole-exome sequencing 030220 oncology & carcinogenesis Gene mutations WES whole exome sequencing Research Article Biotechnology FAT1 PA/IVS Pulmonary atresia with intact ventricular septum HNRNPC lcsh:Biotechnology PPI protein–protein interactions Biophysics MAF minor allele frequency DNA sequencing 03 medical and health sciences lcsh:TP248.13-248.65 CTD Conotruncal defect ComputingMethodologies_COMPUTERGRAPHICS 030304 developmental biology business.industry PA/VSD Pulmonary atresia with ventricular septal defect Rare variants medicine.disease STRING Search Tool for the Retrieval of Interacting Genes business FDR False discovery rates |
| Zdroj: | Computational and Structural Biotechnology Journal Computational and Structural Biotechnology Journal, Vol 18, Iss, Pp 381-392 (2020) |
| ISSN: | 2001-0370 |
| DOI: | 10.1016/j.csbj.2020.01.011 |
| Popis: | Graphical abstract Pulmonary atresia (PA) is a rare congenital heart defect (CHD) with complex manifestations and a high mortality rate. Since the genetic determinants in the pathogenesis of PA remain elusive, a thorough identification of the genetic factors through whole exome sequencing (WES) will provide novel insights into underlying mechanisms of PA. We performed WES data from PA/VSD (n = 60), PA/IVS (n = 20), TOF/PA (n = 20) and 100 healthy controls. Rare variants and novel genes were identified using variant-based association and gene-based burden analysis. Then we explored the expression pattern of our candidate genes in endothelium cell lines, pulmonary artery tissues, and embryonic hearts. 56 rare damage variants of 7 novel candidate genes (DNAH10, DST, FAT1, HMCN1, HNRNPC, TEP1, and TYK2) were certified to have function in PA pathogenesis for the first time. In our research, the genetic pattern among PA/VSD, PA/IVS and TOF/PA were different to some degree. Taken together, our findings contribute new insights into the molecular basis of this rare congenital birth defect. |
| Databáze: | OpenAIRE |
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