Distribution of the Warmblood Fragile Foal Syndrome Type 1 Mutation (PLOD1 c.2032G>A) in Different Horse Breeds from Europe and the United States

Abstract

Warmblood fragile foal syndrome (WFFS) is an autosomal recessive disorder caused by a single nucleotide variant in the procollagen-lysine-2-oxoglutarate-5-dioxygenase 1 gene (PLOD1:c.2032G>A, p.Gly678Arg). Homozygosity for the PLOD1 variant causes an Ehler-Danlos-like syndrome, which has to date only been reported in warmblood breeds but the WFFS allele has been also detected in the Thoroughbred. To investigate the breed distribution of the WFFS allele, 4081 horses belonging to 38 different breeds were screened. In total, 4.9% of the horses representing 21 breeds carried the WFFS allele. The affected breeds were mainly warmbloods, with carrier frequency as high as 17% in the Hanoverian and Danish Warmblood. The WFFS allele was not detected in most non-warmblood breeds. Exceptions include WFFS carriers in the Thoroughbred (17/716), Haflinger (2/48), American Sport Pony (1/12), and Knabstrupper (3/46). The origin of the WFFS allele remains unknown. The Arabian breed and specifically the stallion Bairactar Or. Ar. (1813), whose offspring were reported to have a similar phenotype in the 19th century, were hypothesized as the origin. DNA from a museum sample of Bairactar Or. Ar. showed that he did not carry the mutated allele. This result, together with the genotypes of 302 Arabians, all homozygous for the reference allele, does not support an Arabian origin of the WFFS allele. Our extensive survey shows the WFFS allele to be of moderate frequency and concern in warmbloods and also in breeds where it may not be expected.

Warmblood fragile foal syndrome causative single nucleotide polymorphism frequency in horses in Ireland

“…The frequency of the WFFS mutation in the sport horse population tested in this study (1.98%) is low in comparison to the reported frequency (11-15%) in Warmblood breeds in mainland Europe, the United States and Brazil [13,16,23] While one of the sport horse carriers in this study was reported to be of Warmblood pedigree, most sport horses tested were reported to be 'Irish Sport Horses' . The low frequency of the WFFS allele in sport horses in Ireland may be due to the influence of the traditional Irish Draught and Thoroughbred breeds on the modern Irish Sport Horse.…”

“…Similar carrier frequencies have been reported in Warmbloods in Europe [11,13]. More recently, a higher WFFS allele carrier frequency of 17% in the Hanoverian and Danish Warmblood breeds was described [16], while Metzger et al reported a carrier frequency of 28% in Hanoverian horses in Germany [20]. In a further study, 2.4% of Thoroughbreds in the United States (n = 716) were identified as carriers of the allele [14].…”

“…Recent research demonstrated that the Arabian stallion Bairactar Or. Ar (1813), also hypothesized to be the origin of the WFFS allele, was not the source of the mutation and did not support the hypothesis that the mutation originated in the Arabian breed [16]. Pedigree analysis for genotyped genetic carriers across multiple generations resulted in the identification of a Hanoverian stallion born in 1861 as the most recent common ancestor of investigated carriers [20] but it has been hypothesized that the origin of the mutation can be traced further back to the Thoroughbred breed, which has contributed significantly to today's Warmblood population [22].…”

“…More recently, genotyping of 146 Thoroughbreds from Poland revealed all to be homozygous for the wild type allele (N/N); however, this was a regionally restricted sample [16].…”

“…To date, two gene defects causing EDLS phenotypes in horses have been discovered, hereditary equine regional dermal asthenia (HERDA), a degenerative inherited autosomal recessive skin disorder occurring in Quarter Horses and related breeds [10], and Warmblood fragile foal syndrome (WFFS), a lethal congenital autosomal recessive disorder, which to date has only been reported in Warmblood foals [11,12]; however, the WFFS causative mutation has been identified in Thoroughbreds [13,14], Draft Horses, Paint Horses, Quarter Horses [15] and in the American Sport Pony [16].…”