Will selection for elasticity maintain the allele causing fragile foals

Warmblood Fragile Foal Syndrome (WFFS) is an autosomal monogenic disease leading to a defective connective tissue, which in turn causes skin and mucosa lacerations, fragile skin, hyperextension of the articulations and hematoma. The WFFS is caused by a recessive lethal missense point mutation in the procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 1 gene (PLOD1, c.2032G>A). Foals homozygous for the WFFS recessive allele are not viable, and either aborted during late gestation, or have to be euthanized shortly after birth. Despite its harmful effect, a relatively high WFFS carrier frequency has been found among Warmblood breeds, suggesting a heterozygote advantage. Thus, the aims of this study were 1) estimate WFFS carrier frequency in the Swedish Warmblood breed (SWB), 2) evaluate the effect of WFFS genotype on estimated breeding values, and 3) simulate the potential effects of balancing selection and different selection strategies on future carrier frequency. The WFFS carrier frequency calculated from a cohort of 511 randomly selected SWB horses born in 2017 was equal to 7.4%, whereas it ranged from 0.0% to 14.0% among the whole set of tested SWB (1811 horses) divided into 8 birth year classes starting from 1980 till 2019. Overall, we found a favourable effect of the WFFS allele for movements and dressage traits, highlighting potential balancing selection on the WFFS allele in SWB horses bred for dressage purposes. Via simulations, we proved that balancing selection could maintain a recessive lethal over generations in populations similar to the SWB breed. The allele frequency of a recessive lethal allele is expected to slowly decline over generations but will decrease slower in the presence of balancing selection. Finally, we demonstrated that selection against carrier sires can over time give a more rapid decrease of the mutant allele frequency. Further research is needed to confirm the noticeable association between equine performance and the WFFS genotype. Identification of such associated genetic markers or novel causative mutations to horse performance traits might serve as new tools in horse breeding to select for healthy, sustainable, and better performing horses.