Etalon Discovers Fragile Foal Syndrome in a Wider Variety of Breeds

Fragile Foal Syndrome (FFS), originally termed Warmblood Fragile Foal Syndrome, is an autosomal recessive lethal genetic disorder. Homozygous foals, not aborted or stillborn, exhibit clinical signs including skin lesions, incomplete closure of the abdominal wall, hyper-flexion/extension of joints, inability to stand and difficulty breathing, and usually die or require euthanasia within 72 hours of birth. Genetic testing for FFS has been commercially available since 2013. Initially, it was assumed that FFS was only found in Warmbloods and related breeds, but recent studies have identified FFS-positive Thoroughbreds. The aim of this work was to make unbiased observations of the frequency of FFS across horse breeds.

The DNA of 7,362 horses submitted for commercial genetic testing was genotyped for FFS using hair, tissue, semen or blood samples with owner consent. The population of horses was thinned of related horses within one generation, yielding 7,343 horses representing 78 breeds or types of horse (Table 1).

Using this unbiased testing approach, we observed FFS in a wide group of horse breeds. Among the sampled population of 7,343 horses of various breeds, the overall FSS frequency was 0.56%. The FFS frequency in Warmblood type breeds was 5.32 and 0.45% in other breeds (Table 1 and Table S1). Metzger and colleagues suggest that FFS originated in the W/F-line of Hanoverian warmblood horses. In this study, we observed FFS carriers among diverse populations with no identifiable common ancestor. These new data suggest that the founder of this mutation is much older than proposed by Metzger et al. In previous studies completed in Germany, Brazil and the United States, a carrier frequency of around 10% suggested that more affected foals should be born each year than are reported, but there are no studies exploring the frequency of homozygosity of FFS among stillborns and abortions, nor are breeders accustomed to using genetic testing to explore the reasons for these losses. Thus, the potential economic impact of this variant on the breeding industry cannot yet be reliably estimated.

In addition to our population of unrelated horses, we genotyped a small family consisting of 16 offspring and sired by an American Paint Horse stallion carrying FFS. Within this family, we observed 10 (62.5%) FFS carriers, demonstrating transmission of FFS. Awareness that FFS is not specific to one breed, and the utilization of comprehensive unbiased genetic testing approaches, will aid in the education of breeders and registries for all breeds. Testing can then be appropriately employed, allowing breeders to be more informed when selecting mating pairs and reducing the risk of affected foals and failed pregnancies. This knowledge will help registries to refine policies requiring testing prior to breeding, further ensuring the avoidance of the production of homozygous FFS offspring, and thus reducing the variant frequency in populations.

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Fragile Foal Syndrome (PLOD1 c.2032G>A) occurs across diverse horse populations

Katie Martin*, Samantha Brooks† , Micaela Vierra*, W. Tyler Lafayette*, Scott McClure, Meredith Carpenter* and Christa Lafayette*