UC Davis Research Behind New Test for Atypical Equine Thrombasthenia (AET)
The UC Davis Veterinary Genetics Laboratory (VGL) recently announced the launch of two new genetic tests designed to identify platelet dysfunction disorders that affect horses: Atypical Equine Thrombasthenia (AET) and Glanzmann Thrombasthenia (GT).
Atypical Equine Thrombasthenia (AET) is a recessive platelet disorder that affects Thoroughbred horses. The newly available test is the result of research led by Dr. Carrie Finno, professor and Gregory L. Ferraro Endowed Director of the Center for Equine Health at the UC Davis Weill School of Veterinary Medicine, and her former graduate student, Dr. Anna Dahlgren.
The study identified a missense variant in the Suppressor/Enhancer of Lin-12-like (SEL1L) gene associated with AET in affected Thoroughbreds. Functional studies performed in collaboration with Dr. Jordan Shavit at the University of Michigan Medical School, using human cell lines, along with analyses in knockout mice and zebrafish, confirmed a novel role of SEL1 in platelet function, supporting the identified missense variant as the cause of AET in the affected horses. This discovery was recently highlighted by human physicians for utilizing a multispecies investigation to identify a previously unrecognized component of platelet function.
Platelets are cell fragments in the blood that help stop bleeding by binding fibrinogen and causing clotting. Horses with AET have abnormal clotting, which results in prolonged bleeding after injury.
The development of a genetic test for AET allows owners and breeders to identify affected horses, thereby facilitating informed management and breeding decisions.
This exciting finding is the result of a 20-year long collaboration between myself and Drs. Fern Tablin and Gregory Ferraro,” notes Finno. “In 2005, Dr. Tablin’s team performed detailed analyses of platelets from the first horse described with AET. With the availability of whole-genome sequencing, Dr. Dahlgren was able to identify the likely mutation during her PhD training. Being able to test for AET will be important for the diagnosis of prolonged bleeding in Thoroughbreds.”
At this time, AET has only been identified in Thoroughbred horses. The frequency of the variant in the population is not yet known but is expected to be low.
Another platelet disorder in horses that was first reported in 2007 is Glanzmann Thrombasthenia. This disease occurs in Thoroughbreds through a different genetic mechanism. Two variants in the integrin αIIbβ3 (ITGA2B) gene have been shown to cause Glanzmann Thrombasthenia in affected Thoroughbreds, Quarter Horses, Peruvian Pasos and Oldenburgs. Please visit https://vgl.ucdavis.edu/test/gt for more information.