title: Identification, evolution, and association study of a novel promoter and first exon of the human NOD2 (CARD15) gene.
abstract: Mutations in the NOD2 (CARD15) gene predispose to Crohn's disease (CD), a human chronic inflammatory bowel disorder, and can cause Blau syndrome. During an investigation of an apparent correlation between a frameshifting mutation in the canonical first exon of NOD2 of marmoset and tamarin species and their susceptibility to chronic colitis, we found that, contrary to previous reports, the basal levels of NOD2 transcripts in tissues relevant to CD arise from a distinct novel promoter and first exon. The canonical first exon, by contrast, seems to be of negligible transcriptional importance under physiological conditions, and its reading frame has been disrupted twice during primate evolution. Thus the main NOD2/CARD15 protein isoform produced in humans and other primates is 27 amino acids shorter than previously reported, starting at a conserved methionine in exon 2. We show that there is no significant association between variants in the novel NOD2 promoter region and CD.
authors.affiliation: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, UK.
authors.forename: Kathy
authors.initials: K
authors.lastname: King
authors.forename: Richard
authors.initials: R
authors.lastname: Bagnall
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Faisal
authors.initials: F
authors.lastname: Sheikh
authors.forename: Andrew
authors.initials: A
authors.lastname: Cuthbert
authors.forename: Sipin
authors.initials: S
authors.lastname: Tan
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Mundy
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.forename: Roland G
authors.initials: RG
authors.lastname: Roberts
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003424:Crohn Disease / Q000235:genetics*; D019143:Evolution, Molecular; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016366:Open Reading Frames; D010802:Phylogeny; D011323:Primates / Q000235:genetics; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D020033:Protein Isoforms