title: Identification of susceptibility genes in non-syndromic cleft lip with or without cleft palate using whole-exome sequencing.
abstract: BACKGROUND
  Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P.
  
  
  METHODS
  Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing.
  
  
  RESULTS
  By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples.
  
  
  CONCLUSIONS
  We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P.
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tongshan Road. Xuzhou, Jiangsu, 221004, China, lichunxu2002@163.com.
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhou
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Pan
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Zhang
authors.forename: Qin-Rong
authors.initials: QR
authors.lastname: Wu
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Li
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Xia
authors.forename: Xiu
authors.initials: X
authors.lastname: Peng
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Yu
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Xu
mesh_terms: D001483:Base Sequence; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D059472:Exome; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide