Equine performance genes and the future of doping in horseracing

Abstract

A horse's success on the racetrack is determined by genetics, training and nutrition, and their translation into physical traits such as speed, endurance and muscle strength. Advances in genetic technologies are slowly explaining the roles of specific genes in equine performance, and offering new insights into the development of novel therapies for diseases and musculoskeletal injuries that cause early retirement of many racehorses. Gene therapy approaches may also soon provide new means to artificially enhance the physical performance of racehorses. Gene doping, the misuse of gene therapies for performance enhancement, is predicted to be the next phase of doping faced by horseracing. The risk of gene doping to human sports has been recognised for almost 15 years, and the introduction of the first gene doping detection tests for doping control in human athletes is imminent. Gene doping is also a threat to horseracing, but there are currently no methods to detect it. Efficient and accurate detection methods need to be developed to deter those looking to use gene doping in horses and to maintain the integrity of the sport. Methods developed for human athletes could offer an avenue for detection in racehorses. Development of an equine equivalent test will first require identification of equine genes that will likely be targeted by gene doping attempts. This review focuses on genes that have been linked to athletic performance in horses and, therefore, could be targeted for genetic manipulation. The risks associated with gene doping and approaches to detect gene doping are also discussed.

Droplet Digital PCR Detection of the Erythropoietin Transgene from Horse Plasma and Urine for Gene-Doping Control

“…These results demonstrated the efficacy of this method to detect at least 130 and 200 copies of the EPO transgene in 1 mL plasma and urine, respectively. These procedures might be applicable for other transgenes, such as insulin-like growth factor 1 and follistatin , which are also potential targets for gene-doping in racehorses [4].…”

“…Prohibited substances identified for doping control include low-molecular-weight compounds, such as β-agonists and steroids [2,3]. However, recent developments in veterinary medicine have resulted in genetic doping (i.e., the illegal use of gene therapy) becoming a concern in the horseracing industry [4]. In 2017, the International Federation of Horseracing Authority revised their regulations on gene therapy used in racehorses for the purpose of gene-doping control (), with “administration of oligomers and polymers of nucleic acids and nucleic acid analogues” stipulated as gene therapy in racehorses.…”

Detection of intra‐articular gene therapy in horses using quantitative real time PCR in synovial fluid and plasma

“…Gene therapy is prohibited in equine athletes by regulatory bodies due to the high potential for abuse if used to overexpress performance enhancing genes 4 . Most proteins generated are likely to be physiologically and functionally indistinguishable from endogenous proteins.…”

Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection

“…Genetic therapy is defined as “the administration of oligomers or polymers of nucleic acid and nucleic acid analogues”. In this context, polymers of nucleic acids and their analogues are considered as transgenes [ 3 , 4 ], which have been linked to athletic performance in horses [ 5 ]. Therefore, the development of detection methods for these polymers is important to control gene doping.…”