title: Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using Ingenuity Pathway Analysis®.
abstract: BACKGROUND
  Recurrent airway obstruction (RAO) is a severe chronic respiratory disease affecting horses worldwide, though mostly in the Northern hemisphere. Environmental as well as genetic factors strongly influence the course and prognosis of the disease. Research has been focused on characterization of immunologic factors contributing to inflammatory responses, on genetic linkage analysis, and, more recently, on proteomic analysis of airway secretions from affected horses. The goal of this study was to investigate the interactions between eight candidate genes previously identified in a genetic linkage study and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from healthy and RAO-affected horses. The analysis was carried out with Ingenuity Pathway Analysis® bioinformatics software.
  
  
  RESULTS
  The gene with the greatest number of indirect interactions with the set of proteins identified is Interleukin 4 Receptor (IL-4R), whose protein has also been detected in BALF. Interleukin 21 receptor and chemokine (C-C motif) ligand 24 also showed a large number of interactions with the group of detected proteins. Protein products of other genes like that of SOCS5, revealed direct interactions with the IL-4R protein. The interacting proteins NOD2, RPS6KA5 and FOXP3 found in several pathways are reported regulators of the NFκB pathway.
  
  
  CONCLUSIONS
  The pathways generated with IL-4R highlight possible important intracellular signaling cascades implicating, for instance, NFκB. Furthermore, the proposed interaction between SOCS5 and IL-4R could explain how different genes can lead to identical clinical RAO phenotypes, as observed in two Swiss Warmblood half sibling families because these proteins interact upstream of an important cascade where they may act as a functional unit.
authors.affiliation: Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Berne, Berne, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Racine
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Gerber
authors.forename: Marybeth Miskovic
authors.initials: MM
authors.lastname: Feutz
authors.forename: C Paige
authors.initials: CP
authors.lastname: Riley
authors.forename: Jiri
authors.initials: J
authors.lastname: Adamec
authors.forename: June E
authors.initials: JE
authors.lastname: Swinburne
authors.forename: Laurent L
authors.initials: LL
authors.lastname: Couetil
mesh_terms: D000402:Airway Obstruction / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D019295:Computational Biology / Q000379:methods*; D005786:Gene Expression Regulation / Q000276:immunology; D023281:Genomics / Q000379:methods; D006734:Horse Diseases / Q000235:genetics* / Q000276:immunology*; D006736:Horses; D040901:Proteomics / Q000379:methods; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D019948:Receptors, Interleukin-4; D050826:Suppressor of Cytokine Signaling Proteins