Investigating the Genetic Basis of Fractures in Thoroughbred Racehorses, using a Two Pronged Approach

Fractures in racehorses are a significant economical and welfare concern for the racing industry and can present an adverse front of racing to the general public. Fracture is the main cause of euthanasia on the racecourse, accounting for 60% of all racecourse fatalities. Reducing the incidence of fracture presents a major opportunity to improve the health and welfare of the Thoroughbred horse population.

Four thoroughbreds (two fracture cases, two no-fracture controls) were whole genome sequenced to identify novel mutations associated with fracture risk. A subset of the segregating mutations were chosen for TaqMan genotyping and validation in a larger cohort of samples (cases and controls).

Alongside this, an approach using induced pluripotent stem cells (iPSCs) from genetically high and low risk horses was carried out. The iPSCs will be differentiated into bone in both 2D and 3D culture systems to enable us to understand the biology behind the genetics.

Mutations which segregate between all cases and controls will then be selected for further functional studies (such as expression analysis) within our iPSC bone constructs.

The ultimate aim of the project is to identify the biological mechanisms which underpin the genetic risk of fracture and to refine a genetic test for fracture risk. The information will assist owners, breeders and trainers such that training and racing regimes of high risk horses can be tailored and informed breeding decisions made to reduce the prevalence of fracture in Thoroughbred racehorses.