Genetic risk factors for orthopaedic disease in the Thoroughbred

Orthopaedic disease can occur in Thoroughbred horses at different stages in their life. Conditions seen in the growing foal, classed as developmental orthopaedic disorders, include osteochondrosis, angular limb deformities, physitis and juvenile osteoarthritis. Developmental orthopaedic disorders are a significant world-wide problem in Thoroughbred populations. In Ireland around 11% of foals require treatment for angular limb deformities and physitis [1]. In Australian Thoroughbreds the prevalence of osteochondrosis was estimated to be 23% [2]. Once horses begin training, musculoskeletal injuries are the main reason for horses failing to train or race [3]. Prevalence estimates in the Hong Kong Thoroughbred population suggest that tendon injury (19%) and fracture (13%) are the most common problems, followed by suspensory ligament injury (10%) and osteoarthritis (10%) [4]. Similar prevalences for fracture, tendon and suspensory ligament injury have been reported in the UK Thoroughbred population [5,6].
Most orthopaedic diseases of significance in the Thoroughbred are complex, arising as a result of a combination of genetic risk and environmental factors. The genetic risk comprises the effects of several genes, interacting with each other and the environment. Heritability estimates attempt to partition the observed variation in risk among individuals into genetic and environmental variation. Heritability of osteochondrosis in Thoroughbreds has been estimated at between 0.35 and 0.49 [2]. A genome-wide association study using high density genotyping technology has identified a region on chromosome 3 associated with osteochondrosis, significant at the genome-wide level, in American Thoroughbreds [7]. Significant heritability estimates have also been obtained for distal limb fracture (0.21– 0.37) and superficial digital flexor tendon injury (SDFT) (0.31– 0.34) in UK Thoroughbreds [8]. In addition, there is evidence that fracture and SDFT are positively genetically correlated, suggesting that the genetic risk for the 2 conditions may be a result of shared genetic pathways. DNA-based studies using the latest genotyping technologies are helping to identify the genes underlying fracture risk. Genome regions significantly associated with distal limb fracture have been identified on chromosomes 1 and 18 [9], highlighting several plausible candidate genes. The rapid development of technology is providing new approaches to understanding the basis of genetic risk. For example, the use of whole genome sequencing and functional approaches using in vitro models derived from induced pluripotent stem (iPS) cells herald a new era in developing our understanding of the genetic mechanisms underlying fracture risk in horses. Orthopaedic diseases have been shown to be heritable in multiple species, from mouse to man, so it should be no surprise that genes play a role in the risk of equine orthopaedic disease. Identification of the genes implicated in disease risk will aid in the understanding of how the condition arises. However, larger, more powerful, studies are needed in order to identify how genetic pathways are constructed, and how genes and environmental factors interact. The benefit to veterinary science will be an improved understanding of how susceptible individuals should be managed, and the prospect of new therapies or drugs to aid treatment when disease occurs.
The opportunity to employ breeding strategies aimed at reducing the prevalence of orthopaedic disease should not be ignored. The pig and poultry industries provide examples of how selection for health and performance can be incorporated into the breeding programme, leading to improved animal welfare. In poultry 25 years of selection for improved leg health has led to a significant decrease in the prevalence of orthopaedic disorders [10]. This is despite the unfavourable correlation with body weight and growth rate, traits which have also been under selection. Several studies in pigs have elucidated our understanding of osteochondrosis, and how selection can affect both health and performance. Welfare concerns are of primary interest in agricultural species and animals employed in sporting endeavour are not exempt from these concerns. It is time for the Thoroughbred racing and breeding industry to embrace the new technologies available to them. A focus on breeding strategies to reduce disease prevalence and improve welfare should be encouraged.