title: On the level: IRGM gene function is all about expression.
abstract: Crohn disease is a complex, multigenic, chronic inflammatory bowel disease of uncertain etiology. Recent advances in genetics, including high-throughput single-nucleotide polymorphism typing platforms and deep sequencing technologies have begun to shed light upon disease predisposition and pathogenesis. Autophagy is emerging as a key player in both innate and adaptive immunity, as well as tissue homeostasis and development in the gut. Here we describe our recent studies into the Crohn disease-associated Immunity-Related GTPase family, M (IRGM) gene and our discovery of a large risk-conferring upstream deletion. We discuss the effects of this deletion upon expression levels of IRGM alleles and how tissue-specific expression might be affected by the promoter polymorphism. In addition, we comment upon the potential roles of IRGM in autophagy of intracellular pathogens, and the challenges ahead for further elucidating IRGM function.
authors.affiliation: Gastrointestinal Unit and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Huett
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D003424:Crohn Disease / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D019204:GTP-Binding Proteins; C513539:IRGM protein, human