Norton Elaine M, Mickelson James R, Binns Matthew M, Blott Sarah C, Caputo Paul, Isgren Cajsa M, McCoy Annette M, Moore Alison, Piercy Richard J, Swinburne June E, Vaudin Mark, McCue Molly E
From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
J Hered. 2016 Nov;107(6):537-43. doi: 10.1093/jhered/esw042. Epub 2016 Aug 3.
Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise. The objective was to evaluate the importance of genetic factors in RER by obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility.
纯种马和标准赛马的复发性运动性横纹肌溶解症（RER）的特征是肌肉僵硬和细胞损伤发作，常在剧烈运动时复发。目的是通过对无关的纯种马和标准赛马群体的遗传力进行无偏估计，来评估遗传因素在RER中的重要性。491匹纯种马和196匹标准赛马使用54K或74K SNP基因分型芯片进行基因分型。利用标准遗传关系矩阵（GRM），通过混合线性和贝叶斯模型从全基因组SNP数据中计算遗传力。在调整疾病患病率和性别后，混合线性模型和贝叶斯模型估计纯种马RER的遗传力约为0.34，标准赛马的遗传力约为0.45。为了考虑潜在因果变异的遗传结构差异，基于连锁不平衡加权亲属矩阵、次要等位基因频率和变异效应大小对遗传力估计值进行调整，得到的遗传力估计值在0.41 - 0.46（纯种马）和0.39 - 0.49（标准赛马）之间。总之，纯种马和标准赛马RER易感性变异分别有34% - 46%和39% - 49%可由这两种基因分型芯片上的SNP解释，表明RER具有中度遗传性。这些数据为研究与RER易感性相关的基因突变提供了进一步的理论依据。
