Evaluation of genetic risk factors for Recurrent Airway Obstruction in European warmblood horses
|Director of thesis||Prof. Tosso Leeb|
|Co-director of thesis|
|Summary of thesis||
Recurrent airway obstruction (RAO) or “heaves” is one of the most common airway diseases affecting mature horses worldwide. The condition is characterized clinically by reversible bronchoconstriction, increased mucus production and neutrophilic airway inflammation following exposure of susceptible horses to antigens and endotoxins present in hay and stable dust (Cunningham and Dunkel, 2008; Léguillette, 2003). Equine RAO is a naturally occurring respiratory disease in horses with many similarities to human asthma and, as a result, has been used as an animal model of this disease (Deaton, 2006). Acute and chronic inflammation of the airway remains an important health problem for equids. RAO remains one of the most commonly diagnosed conditions affecting the lung of older horses in Europe and the United States (Horohov et al, 2005). RAO has a familial basis and shows a complex mode of inheritance (Marti et al, 1991; Ramseyer et al, 2007; Gerber et al, 2009). The exact mechanism underlying the development of RAO is not yet known, as both genetics and environment play an important role.
The equine clinic at the University of Bern has collected more than 400 Warmblood horses with very detailed phenotypes. Recently our collaboration partner (the Animal Health Trust, in the UK) performed a QTL analysis in two paternal half-sib families. For the QTL analysis ~250 microsatellites, evenly spaced throughout the genome, were genotyped in all horses in these families. Linkage of various phenotypic traits such as e.g. overall clinical score, coughing, and nasal discharge with the different markers has been analyzed. The analyses resulted in the identification of two chromosome regions showed a genome-wide linkage. In each family only one QTL was detectable indicating possible heterogeneity of the genetic risk factors. The QTL in family 1 spanned 22 Mb on chromosome 13, the QTL in family 2 spanned 31 Mb on chromosome 15 (Swinburne et al, 2009). Of these QTLs, the QTL on chr13 is more preferable because of its best signaling, smaller distance and more related genes to immune system.
During this PhD project positional and functional candidate genes for RAO shall be further investigated. The ultimate goal would be the identification of causative DNA variations contributing to the RAO risk of a horse.
|Administrative delay for the defence|