A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

BMC Genomics

Mark Vaudin²  J Richard Newton²  Tim DH Parkin¹  Lynn Hillyer³  Maud Helwegen²  Laura Y Fox-Clipsham²  Charlene Sibbons²  June E Swinburne²  Sarah C Blott² 

[1]Present address: Boyd Orr Centre for Population and Ecosystem Health, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK

[2]Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK

[3]British Horseracing Authority, 75 High Holborn, London WC1V 6LS, UK

关键词: Genetic variation;    Genome-wide association;    Horse;    Fracture risk;   

Others  :  1217849
DOI  :  10.1186/1471-2164-15-147

 received in 2012-08-21, accepted in 2014-02-14,  发布年份 2014

【 摘 要 】

Background

Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse.

Results

Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the same time period as the cases, and had no history of fracture at the time the study was carried out. The horses sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs were employed to perform a genome-wide association analysis and to estimate the proportion of genetic variance attributable to the SNPs on each chromosome using restricted maximum likelihood (REML). Significant genetic variation associated with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on chromosome 18 (62.05 Mb – 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb) reached genome-wide significance (p < 0.05) in a genome-wide association study (GWAS). Two of the SNPs on ECA 18 were located in a haplotype block containing the gene zinc finger protein 804A (ZNF804A). One haplotype within this block has a protective effect (controls at 1.95 times less risk of fracture than cases, p = 1 × 10^-4), while a second haplotype increases fracture risk (cases at 3.39 times higher risk of fracture than controls, p = 0.042).

Conclusions

Fracture risk in the Thoroughbred horse is a complex condition with an underlying genetic basis. Multiple genomic regions contribute to susceptibility to fracture risk. This suggests there is the potential to develop SNP-based estimators for genetic risk of fracture in the Thoroughbred racehorse, using methods pioneered in livestock genetics such as genomic selection. This information would be useful to racehorse breeders and owners, enabling them to reduce the risk of injury in their horses.

【 授权许可】

   
2014 Blott et al.; licensee BioMed Central Ltd.

【 图 表 】

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