Identification of a global gene expression signature associated with the genetic risk of catastrophic fracture in iPSC-derived osteoblasts from Thoroughbred horses

Palomino Lago, Esther; Ross, Amy; McClellan, Alyce; Guest, Deborah

Abstract

Bone fractures are a significant problem in Thoroughbred racehorses. The risk of fracture is influenced by both genetic and environmental factors. To determine the biological processes that are affected in genetically susceptible horses, we utilised polygenic risk scoring to establish induced pluripotent stem cells (iPSCs) from horses at high and low genetic risk. RNA-sequencing on iPSC-derived
osteoblasts revealed 112 genes that were significantly differentially
expressed. Forty-three of these genes have known roles in bone, 27 are not yet annotated in the equine genome and 42 currently have no described role in bone. However, many of the proteins encoded by the known and unknown genes have reported interactions. Functional enrichment analyses revealed that the differentially expressed genes were overrepresented in processes regulating the extracellular matrix and pathways known to be involved in bone remodelling
and bone diseases. Gene set enrichment analysis also detected numerous biological processes and pathways involved in glycolysis with the associated genes having a higher expression in the iPSC-osteoblasts from horses with low polygenic risk scores for fracture. Therefore, the differentially expressed genes may be relevant for maintaining bone homeostasis and contribute to fracture risk. A deeper understanding of the consequences of mis-regulation
of these genes and the identification of the DNA variants which underpin their differential expression may reveal more about the molecular mechanisms which are involved in equine bone health and fracture risk.

Citation

Palomino Lago, E., Ross, A., McClellan, A., & Guest, D. (2025). Identification of a global gene expression signature associated with the genetic risk of catastrophic fracture in iPSC-derived osteoblasts from Thoroughbred horses. Animal Genetics, https://doi.org/10.1111/age.13504

• Journal Article Type: Article
• Acceptance Date: Dec 23, 2024
• Online Publication Date: Jan 13, 2025
• Publication Date: Jan 13, 2025
• Deposit Date: Jan 13, 2025
• Publicly Available Date: Jan 23, 2025
• Print ISSN: 0268-9146
• Electronic ISSN: 1365-2052
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/age.13504