Hanoverian F/W-line contributes to segregation of Warmblood fragile foal syndrome type 1 variant PLOD1:c.2032G>A in Warmblood horses.
Authors: Metzger Julia, Kreft Oliver, Sieme Harald, Martinsson Gunilla, Reineking Wencke, Hewicker-Trautwein Marion, Distl Ottmar
Journal: Equine veterinary journal
Summary
Warmblood fragile foal syndrome type 1 (WFFST1) is a lethal condition in Warmbloods caused by a missense variant in the PLOD1 gene (c.2032G>A), which affects collagen cross-linking and manifests as severely degraded collagen architecture in affected foals' skin. Metzger and colleagues validated this variant through whole-genome sequencing and traced its origin to a single stallion from the Hanoverian F/W sire line, revealing an allele frequency of 14% in Hanoverian horses—a concerningly high prevalence for a lethal recessive condition. Necropsy findings confirmed the pathological hallmark: multifocal collagen fibril degradation and abnormal fibrillar plaques throughout the dermis, consistent with defective lysyl hydroxylase function. Notably, the WFFST1 variant showed significant association with improved estimated breeding values for gait quality, conformation and dressage performance, suggesting inadvertent selection pressure toward this deleterious allele through pursuit of desirable movement traits. For equine professionals, these findings underscore the critical importance of implementing genomic testing in Hanoverian breeding programmes—particularly screening carrier status in animals descended from the F/W line—to prevent homozygous conceptions whilst managing the trade-off between eliminating a lethal mutation and preserving valuable performance-linked genetic diversity.
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Practical Takeaways
- •Hanoverian breeders should consider genetic testing for PLOD1:c.2032G>A to identify carrier stallions (F/W-line) and prevent homozygous affected foals, which are lethal
- •The variant's association with improved performance traits suggests selection pressure has inadvertently maintained this mutation in the population; breeding decisions should weigh conformation benefits against lethal risk in homozygotes
- •Affected foals present with severe collagen defects visible on necropsy; breeders of Warmbloods should be aware of this lethal syndrome and its genetic basis for informed breeding decisions
Key Findings
- •PLOD1:c.2032G>A missense variant validated as causative for WFFST1, with allele frequency of 0.14 in Hanoverian horses
- •Hanoverian F/W-line stallion identified as most common recent ancestor of all genetic carriers through pathway analysis
- •Histopathology revealed loosely arranged collagen fibres with multifocal degraded collagen fibrils and fibrillar plaques ultrastructurally
- •WFFST1 variant correlated with improved estimated breeding values for gait-related traits, conformation, and dressage performance