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

Abstract

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

“…Pedigree analyses of Hanoverian WFFS carriers identified one stallion of the traditional sire line F/W as a most recent common ancestor. This stallion, born in 1861, maybe one of the major contributors to the spread of the WFFS allele in warmblood populations [29]. In our study, similarly high numbers of carriers as in the Hanoverian were detected in the Oldenburger (15.5%, 219 horses tested) and the American Warmblood (14.0%, 57 horses tested).…”

“…We detected the WFFS allele in 17 out of 19 tested warmblood breeds, with the highest estimated carrier frequency of 17.3% in the Hanoverian (283 horses) and the Danish Warmblood (127 horses). In a study of 849 Hanoverians, Metzger et al 2020 [ 29 ] reported an allele frequency of 14%, making the expected carrier frequency 24%, which is notably higher than any of the other breeds investigated here. Pedigree analyses of Hanoverian WFFS carriers identified one stallion of the traditional sire line F/W as a most recent common ancestor.…”

“…Nevertheless, there is evidence for the origin of WFFS in the Thoroughbred because of the occurrence of the WFFS allele in this breed and the large influence of Thoroughbreds in warmblood breeds where the allele mainly occurs. However, the suggestion of Wobbe et al, 2019 [ 31 ] that Bay Ronald XX or his son Dark Ronald XX represent the common ancestor of all carriers could not be confirmed in Metzger et al, 2019 [ 29 ]. Indeed, Dark Ronald XX has been excluded as the founder in Zhang et al, 2020 [ 32 ] through DNA testing of skin remains.…”

“…It is proposed to be an autosomal recessive disorder caused by a SNV in the procollagen-lysine-2-oxoglutarate-5-dioxygenase 1 gene (PLOD1:c.2032G>A, p.Gly678Arg) [ 26 , 27 ]. Homozygosity for this PLOD1 variant (WFFS allele) is thought to be incompatible with extra-uterine life with a total of 18 cases described to date in the literature [ 26 , 27 , 28 , 29 ]. The predominant manifestation is death during the later stages of gestation ( n = 4) or live births with foals being non-viable or euthanized because of poor prognosis ( n = 14) [ 28 ].…”

“…Further, the WFFS allele was not associated with catastrophic breakdown [ 30 ]. Most recently, the WFFS allele frequency was estimated to be 14% in Hanoverians [ 29 ]. Pedigree analyses of WFFS carriers in warmbloods suggested that the variant could trace to the English Thoroughbred stallion Dark Ronald, a formative ancestor in many German warmblood lines [ 31 ].…”