Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using ingenuity pathway analysis®
1 Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Berne, Länggassstrasse 124, Berne, 3012, Switzerland
2 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, Indiana, 47907, USA
3 Bindley Bioscience Center, Purdue University, 201 South University Street, West Lafayette, Indiana, 47907, USA
4 Animal Health Trust, Lanwades Hall, Kentford, Newmarket, Suffolk CB8 7UU, UK
BMC Veterinary Research 2011, 7:48 doi:10.1186/1746-6148-7-48Published: 15 August 2011
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.
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.
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.