Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using ingenuity pathway analysis^®

Authors

Julien Racine, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Berne
Vinzenz Gerber, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Berne
Marybeth Miskovic Feutz, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University
C. Paige Riley, Bindley Bioscience Center, Purdue University
Jiri Adamec, University of Nebraska-LincolnFollow
June E. Swinburne, Animal Health Trust, Lanwades Hall, Kentford, Newmarket, Suffolk
Laurent L. Couetil, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue UniversityFollow

Document Type

Article

Date of this Version

2011

Citation

Racine et al. BMC Veterinary Research 2011, 7:48

Comments

This document is published under a Creative Commons/Open Access license.

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 nother 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 NF_kB pathway.

Conclusions: The pathways generated with IL-4R highlight possible important intracellular signaling cascades implicating, for instance, NF_kB. 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.