title: Multiple gene mutations identified in patients infected with influenza A (H7N9) virus.
abstract: Influenza A (H7N9) virus induced high mortality since 2013. It is important to elucidate the potential genetic variations that contribute to virus infection susceptibilities. In order to identify genetic mutations that might increase host susceptibility to infection, we performed exon sequencing and validated the SNPS by Sanger sequencing on 18 H7N9 patients. Blood samples were collected from 18 confirmed H7N9 patients. The genomic DNA was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Genome analysis Tool. SNPs were verified by independent Sanger sequencing. The DAVID database and the DAPPLE database were used to do bioinformatics analysis. Through exon sequencing and Sanger sequencing, we identified 21 genes that were highly associated with H7N9 influenza infection. Protein-protein interaction analysis showed that direct interactions among genetic products were significantly higher than expected (p = 0.004), and DAVID analysis confirmed the defense-related functions of these genes. Gene mutation profiles of survived and non-survived patients were similar, suggesting some of genes identified in this study may be associated with H7N9 influenza susceptibility. Host specific genetic determinants of disease severity identified by this approach may provide new targets for the treatment of H7N9 influenza.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.|Division of Neonatology, Children's Hospital of Fudan University, China.
authors.forename: Mingbang
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, China.
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pulmonary Medicine, Shanghai Jiao-Tong University School of Medicine, China.
authors.forename: Jieming
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Xi
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.
authors.forename: Xiangda
authors.initials: X
authors.lastname: Lao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Seeley
authors.affiliation: Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: BGI-tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Pulmonary Medicine, Qingpu Central Hospital, Fudan University, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.|Division of Neonatology, Children's Hospital of Fudan University, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
authors.affiliation: Department of Pulmonary Medicine, Shanghai Jiao-Tong University School of Medicine, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, China.
authors.forename: Shuihua
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.|Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, China.|Department of Pulmonary Medicine, Qingpu Central Hospital, Fudan University, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.|Division of Neonatology, Children's Hospital of Fudan University, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zhou
mesh_terms: D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005091:Exons / Q000235:genetics; D063990:Gene Ontology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000235:genetics* / Q000821:virology*; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics