title: Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study.
abstract: BACKGROUND
  Genetic variants make some contributions to inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). More than 100 susceptibility loci were identified in Western IBD studies, but susceptibility gene has not been found in Chinese IBD patients till now. Sequencing of individuals with an IBD family history is a powerful approach toward our understanding of the genetics and pathogenesis of IBD. The aim of this study, which focuses on a Han Chinese CD family, is to identify high-risk variants and potentially novel loci using whole exome sequencing technique.
  
  
  METHODS
  Exome sequence data from 4 individuals belonging to a same family were analyzed using bioinformatics methods to narrow down the variants associated with CD. The potential risk genes were further analyzed by genotyping and Sanger sequencing in family members, additional 401 healthy controls (HC), 278 sporadic CD patients, 123 UC cases, a pair of monozygotic CD twins and another Chinese CD family.
  
  
  RESULTS
  From the CD family in which the father and daughter were affected, we identified a novel single nucleotide variant (SNV) c.374T>C (p.I125T) in exon 4 of discs large homolog 1 (DLG1), a gene has been reported to play multiple roles in cell proliferation, T cell polarity and T cell receptor signaling. After genotyping among case and controls, a PLINK analysis showed the variant was of significance (P<0.05). 4 CD patients of the other Chinese family bore another non-synonymous variant c.833G>A (p.R278Q) in exon 9 of DLG1.
  
  
  CONCLUSIONS
  We have discovered novel genetic variants in the coding regions of DLG1 gene, the results support that DLG1 is a novel potential susceptibility gene for CD in Chinese patients.
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China; Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases, and Hubei Key Laboratory of Immune Related Diseases, Wuhan, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, People's Republic of China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Siew Chien
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China; Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases, and Hubei Key Laboratory of Immune Related Diseases, Wuhan, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ran
authors.affiliation: Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases, and Hubei Key Laboratory of Immune Related Diseases, Wuhan, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Wuhan, People's Republic of China; Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases, and Hubei Key Laboratory of Immune Related Diseases, Wuhan, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D003424:Crohn Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D000074288:Discs Large Homolog 1 Protein; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins