Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed

Abstract

Summary Background Catastrophic fractures are among the most common cause of fatalities in racehorses. Several factors, including genetics, likely contribute to increased risk for fatal injuries. A variant in the procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase1 gene (PLOD1 c.2032G>A) was shown to cause Warmblood fragile foal syndrome type 1 (WFFS), a fatal recessive defect of the connective tissue. Screening of multiple horse breeds identified the presence of the WFFS allele in the Thoroughbred. PLOD1 is involved in cross‐linking of collagen fibrils and thus could potentially increase the risk of catastrophic breakdown. Objectives Estimate the frequency of the WFFS allele (PLOD1 c.2032G>A) and determine if it is a risk factor for catastrophic breakdown in the Thoroughbred. Study design Case–control genetic study. Methods Genomic DNA from hair and/or tissue samples was genotyped for the WFFS allele. Fisher’s Exact tests were performed to compare allele and carrier frequencies between the case cohort (catastrophic breakdown, n = 22) and several cohorts with no record of injury (n = 138 raced/trained at same track and season and n = 185 older than 7 years and raced during same season), nonracers (n = 92), and a random sample without consideration for racing history (n = 279). Results The frequency of the PLOD1 c.2032G>A variant in the Thoroughbred breed is low (1.2%). Seventeen of 716 Thoroughbreds tested were carriers (2.4%) and no WFFS homozygotes were detected. Only one catastrophic breakdown case carried the WFFS allele. No statistically significant difference in allele or carrier frequency was identified between case and control cohorts (P>0.05 in all comparisons performed). Main limitations This study evaluated cases from one single track. Conclusions This study demonstrated that the PLOD1 c.2032G>A associated with WFFS is present at very low frequency in Thoroughbreds and is not a genetic risk factor for catastrophic breakdown.

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

“…The occurrence of WFFS carriers in Thoroughbreds has been shown previously to be 2.4% in Bellone et al, 2019 [30], but all 146 Thoroughbreds from Poland genotyped in this study were homozygous for the reference allele (PLOD1:c.2032G).…”

“…The collection includes Thoroughbreds, warmblood horse breeds, Quarter Horses, breeds derived from warmbloods, and breeds in which warmbloods are allowable crosses. The sample set was also supplemented by a large number of Arabians (302), a selection of baroque horses, such as Friesians and Lippizans, and draft and pony breeds ( The 716 Thoroughbred horses included in this study were used in Bellone et al, 2019 [30] and were included here for completeness of the dataset.…”

“…Akhal Teke, Arabian, and the tested gaited breeds (Tennessee Walker and Rocky Mountain Horse) also exclusively showed the reference allele. [30]. Data in italic font denote breeds with small sample sizes (n < 30).…”

Hanoverian F/W‐line contributes to segregation of Warmblood fragile foal syndrome type 1 variant PLOD1:c.2032G>A in Warmblood horses

“…Thoroughbred contributed to about 34.8% to the genes of the Hanoverian population (reference population 1980‐2000) 41 . Furthermore, a genotyping study of 716 Thoroughbred racehorses for WFFST1 variant confirmed that the mutant WFFST1 allele is present in the Thoroughbred population with a relatively low frequency of 1.2% 25 . The transmission of WFFST1 mutant allele from a Thoroughbred horse and the wide distribution in Warmblood horses might therefore be explained by the fact that Thoroughbred stallions which influence Warmblood breeding are no longer used for breeding in the Thoroughbred population.…”

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

“…Genetic testing for FFS has been commercially available since 2013 2 . Initially, it was assumed that FFS was only found in Warmbloods and related breeds, 2 but recent studies have identified FFS‐positive Thoroughbreds 3 . The aim of this work was to make unbiased observations of the frequency of FFS across horse breeds (Figure 1).…”