A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Skin Fibroblast Cell Isolation and Culture
2.2. Polygenic Risk Scoring of Thoroughbred Skin Fibroblasts
2.3. Osteoblast Differentiation
2.4. Histological Staining
2.5. RNA Extraction, cDNA Synthesis, and Quantitative PCR
2.6. Immunocytochemistry
2.7. Whole-Genome Sequencing
2.8. Genotyping for the COL3A1 SNP
2.9. Overexpression of SOX11
2.10. SOX11 Knockdown
2.11. ELISA
2.12. Electrophoretic Mobility Shift Assay (EMSA)
2.13. Construction of the Luciferase Reporter Plasmids
2.14. Luciferase Assays
2.15. Statistical Analysis
3. Results
3.1. Application of a Polygenic Risk Score to Select Thoroughbred Cells for Use
3.2. Skin Fibroblasts Can Differentiate into Osteoblast-like Cells In Vitro
3.3. Candidate Gene Expression Analysis Reveals a Significant Difference in STAT1 and COL3A1 Gene Expression in Skin-Derived Osteoblasts from High- and Low-Risk Thoroughbred Horses
3.4. WGS Revealed a SNP in the Region Upstream of COL3A1 That Is Predicted to Result in the Loss of a SOX11 Binding Site and Is Significantly Associated with Fracture Risk
3.5. SOX11 Is Expressed in Undifferentiated and Osteoblast-Differentiated Skin Fibroblasts but Is Not Differentially Expressed between High- and Low-Risk Horses
3.6. SOX11 Modulation in Skin Fibroblasts Results in Significant Changes in the Expression of COL3A1
3.7. The Region Containing the SNP Binds to Nuclear Proteins from Equine Cells
3.8. The Region Containing the SNP Has Promoter Activity, and the SNP Affects Reporter Gene Expression in a Genetic-Background-Dependent Manner
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Palomino Lago, E.; Baird, A.; Blott, S.C.; McPhail, R.E.; Ross, A.C.; Durward-Akhurst, S.A.; Guest, D.J. A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses. Animals 2024, 14, 116. https://doi.org/10.3390/ani14010116
Palomino Lago E, Baird A, Blott SC, McPhail RE, Ross AC, Durward-Akhurst SA, Guest DJ. A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses. Animals. 2024; 14(1):116. https://doi.org/10.3390/ani14010116
Chicago/Turabian StylePalomino Lago, Esther, Arabella Baird, Sarah C. Blott, Rhona E. McPhail, Amy C. Ross, Sian A. Durward-Akhurst, and Deborah J. Guest. 2024. "A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses" Animals 14, no. 1: 116. https://doi.org/10.3390/ani14010116
APA StylePalomino Lago, E., Baird, A., Blott, S. C., McPhail, R. E., Ross, A. C., Durward-Akhurst, S. A., & Guest, D. J. (2024). A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses. Animals, 14(1), 116. https://doi.org/10.3390/ani14010116