Selection signature analyses and genome‐wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis
Authors: M. Momen, S. Brounts, Emily E. Binversie, Susannah J. Sample, G. Rosa, Brian W. Davis, P. Muir
Journal: G3: Genes|Genomes|Genetics
Summary
# Editorial Summary Degenerative suspensory ligament desmitis (DSLD) carries substantial breed predisposition, with Peruvian Horses facing markedly elevated risk whilst ponies and draft breeds remain largely unaffected, yet the underlying genetic architecture has remained unclear until now. Momen and colleagues analysed 670,000 genetic variants across ten horse breeds stratified by DSLD risk category, employing genome-wide association and selection signature analysis to identify the molecular mechanisms driving breed susceptibility. The research revealed DSLD as a polygenic condition with positive selection signatures on chromosomes 7, 18, and 23, implicating genes governing mechanotransduction (KANK1, KANK2, JUNB, SEMA7A), collagen synthesis (COL4A1, COL5A2, COL5A3, COL6A5), aging responses in tendon tissue (PIN1), hypoxia-mediated matrix remodelling (PRDX2), and BMP signalling—collectively pointing to disrupted suspensory ligament homeostasis under mechanical loading rather than impaired proteoglycan turnover. For practitioners, these findings suggest that selective breeding away from high-risk variants may be achievable in predisposed populations, whilst the mechanotransduction and collagen-synthesis pathways represent potential targets for therapeutic intervention to mitigate disease progression in affected horses.
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Practical Takeaways
- •Peruvian Horse owners and breeders should be aware of significantly elevated genetic risk for DSLD; screening breeding stock and careful management of mechanical loading in young horses is warranted
- •Understanding the mechanotransduction and collagen synthesis pathways implicated suggests potential therapeutic targets related to load management, tissue quality optimization, and metabolic support
- •Draft and pony breeds show protective genetic profiles; selective breeding away from high-risk variants in susceptible breeds may be possible with genomic testing
Key Findings
- •DSLD is a polygenic disease with breed-related prevalence, highest in Peruvian Horses and lowest in pony and draft breeds
- •Positive selection signatures identified on chromosomes 7, 18, and 23 associated with DSLD breed risk categories
- •Multiple biological pathways implicated in disease pathogenesis including mechanotransduction (KANK1, KANK2, JUNB, SEMA7A), collagen synthesis (COL4A1, COL5A2, COL5A3, COL6A5), and aging-related factors (PIN1)
- •Disease mechanism involves disturbances to suspensory ligament homeostasis and matrix responses to mechanical loading rather than primary proteoglycan turnover dysfunction