Investigation for Genetic Determinants of Flexion Contractures and Contracted Foal Syndrome in Neonatal Thoroughbred Foals

Musculoskeletal disorders are one of the leading causes of morality in neonatal Thoroughbred foals. Contracted Foal Syndrome (CFS) has accounted for up to 48% of such disorders in foals submitted for necropsy according to the Kentucky Livestock Diagnostic Center and is reportedly a concern to clinicians and breeders. CFS is primarily characterized by limb contractures and other malformations of the appendicular and/or axial skeleton. Foals are often euthanized in severe cases and successful rehabilitation in moderate cases does not entirely negate secondary complications. Because of the economic implications associated with treatment costs, owners may opt to euthanize foals even though they potentially could have led productive lives.

A familial predisposition was observed in some cases. In addition, veterinarians reported increased incidence of contracted foals in one particular sire line. This, coupled with model genetic disorders in other species, prompted us to conduct the first molecular genetics study on congenital flexion and CFS.

The inconsistent nature of clinical documentation and variable phenotypes pose a challenge to researchers investigating such complex conditions. We therefore conducted a detailed analysis of the phenotypes and used the data to propose a preliminary classification system that could be used by clinicians and researchers. The implementation of such a classification system will reduce ambiguity of clinical documentation and provide the basis for future study designs.

Our hypothesis states, that in some cases, flexion contractures and CFS are major gene disorders with the likelihood of genetic heterogeneity. Our first approach was to sequence the candidate gene, tropomyosin beta 2. This gene encodes a component of the skeletal muscle contractile apparatus and has been implicated in congenital distal limb contractures in humans. Next, new utilized the newly available Equine SNP50 Beadchip for a case/control population based genome-wide association mapping approach followed by a family validation study and family based genome-wide association study. These approaches resulted in the identification of associations between various subtypes of contracted foals and at least 3 disease susceptibility loci.

In summary, this study provides insight into the genetics underlying flexion contractures and CFS in the neonatal foal and has proved the first evidence for a genetic cause. Furthermore, it provides a solid foundation for future research targeting candidate genes for resequencing.