Prevalence of the E321G MYH1 variant in Brazilian Quarter Horses

Abstract

Background: In the Quarter Horse (QH), myosin heavy chain myopathy (MYHM), which is characterised by nonexertional rhabdomyolysis or immune-mediated myositis (IMM) with acute muscle atrophy, is strongly associated with the missense E321G MYH1 mutation.Objectives: To document the existence of MYHM in the Brazilian QH population, this study includes a case report of two related QH foals with the E321G MYH1 mutation that had clinical signs of MYHM, with histological confirmation of IMM in one of the foals. This prompted an investigation the aim of which was to determine the allele frequency of the E321G MYH1 variant across QHs using a DNA archive in Brazil. Study design: Cross sectional.Methods: To estimate the allele frequency of the E321G MYH1 variant in Brazilian QHs, 299 DNA samples from QHs used in different disciplines (reining, barrel racing, halter, cutting and racing) were analysed. DNA fragments containing the region with the mutation were amplified by PCR and used for direct genomic sequencing.Results: Of the 299 genotyped QHs, 44 animals (14.7%) were heterozygous (My/N) for the E321G MYH1 variant, and 255 (85.3%) were homozygous for the wild-type allele (N/N), implying an allele frequency of 0.074. Reining horses had a significantly higher prevalence of heterozygosity than horses in other disciplines (P = .008). Main limitations:The DNA samples were collected from 2010 to 2014. As only registered QHs were evaluated, the results may not reflect the actual incidence in the general population of Brazilian QHs. Conclusions:The reported cases of MYHM and the high prevalence of the MYH1 mutation found in the assessed Brazilian QH population, particularly in reining QHs, suggests that MYHM should be included in genetic screening. Reasonable control measures are important to prevent an increase in the incidence of MYHM in QHs in Brazil.

Prevalence of clinical signs and factors impacting expression of myosin heavy chain myopathy in Quarter Horse‐related breeds with the MYH1E321G mutation

“…5,6 Reining and ranch horses had the highest prevalence among performance groups at 21%-22% in agreement with other studies. 5,6 The high prevalence of MYH1 E321G QH in our study likely was influenced by the fact that 63% of participating owners performed genetic testing because their veterinarians recommended it or to screen for genetic disease, as well as by the preponderance of reining and ranch horses in our sample. The benefit of the bias toward horses with MYH1 E321G in our study, however, was that it provided 10 My/My horses to evaluate.…”

“…Overall, the prevalence of MYH1 E321G in our study population was 29%, much higher than the prevalence in random samples of QH at 7%‐15% 5,6 . Reining and ranch horses had the highest prevalence among performance groups at 21%‐22% in agreement with other studies 5,6 .…”

“…The MYH1 E321G homozygotes were not present in random samples of QH with unknown phenotypes in previous studies and only 1 My/My horse was found in random sampling of elite performance horses, validating this approach to identify additional My/My horses essential for investigation of environmental triggers and other factors. 5,6 Although there were more My/My horses in our study than found in random sampling studies, the number of homozygous horses was still relatively small. Nevertheless, we can conclude that clinical signs of MYHM are common in My/My horses, with 8 of 9 developing atrophy and 3 of 10 moderate to severe stiffness.…”

“…Penetrance may be reliant upon activation of autoimmunity by vaccination or infection, as suggested by studies of clinical MYHM cases 1,4 . The need for more information on penetrance and predisposing factors is emphasized by the fact that 7%‐15% of Quarter Horses carry MYH1 E321G 5,6 . Scientific studies of disease probability, performance limitations, and triggering factors for MYHM would assist owners of MYH1 E321G horses in making decisions on breeding, prepurchase and vaccination strategies.…”

“…1,4 The need for more information on penetrance and predisposing factors is emphasized by the fact that 7%-15% of Quarter Horses carry MYH1 E321G . 5,6 Scientific studies of disease probability, performance limitations, and triggering factors for MYHM would assist owners of MYH1 E321G horses in making decisions on breeding, prepurchase and vaccination strategies. The questionnaire included the following sections.…”