Categories: Muscle phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 160750 (trait) , 160730 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Species-specific name: myosin heavy chain myopathy

Species-specific symbol: IMM

Inheritance: Finno et al. (2018): "Pedigree analysis supported either an autosomal dominant or autosomal recessive mode of inheritance."

Mapping: Finno et al. (2018): "A genome-wide association (GWA) study . . . on 36 IMM [Quarter Horses] QHs and 54 breed matched unaffected QHs from the same environment using the Equine SNP50 and SNP70 genotyping arrays . . . identified nine SNPs within a ~ 2.87 Mb region on chr11 that were significantly (Punadjusted < 1.4 × 10− 6) associated with the [immune-mediated myositis] IMM phenotype."

Molecular basis: Finno et al. (2018) reported that "Whole genome sequencing of four IMM and four unaffected QHs identified a single segregating nonsynonymous E321G mutation in [a positional candidate gene] MYH1 encoding myosin heavy chain 2X. Genotyping of additional 35 IMM and 22 unaffected QHs confirmed an association (P = 2.9 × 10− 5), and the putative mutation was absent in 175 horses from 21 non-QH breeds."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Finno et al. (2018): "immune-mediated myositis (IMM) [is] . . . characterized by recurrent, rapid-onset muscle atrophy in Quarter Horses (QH)"

Pathology: Finno et al. (2018): "The histopathologic hallmark of IMM is lymphocytic infiltration of myofibers."

Prevalence: Gianino et al. (2019): "The E321G MYH1 variant allele frequency was 0.034 ± 0.011 in the general QH population (6.8% of individuals in the breed) and the highest among the reining (0.135 ± 0.040; 24.3% of reiners), working cow (0.085 ± 0.031), and halter (0.080 ± 0.027) performance subgroups. The E321G MYH1 variant was present in cutting (0.044 ± 0.022) and Western Pleasure (0.021 ± 0.015) QHs at lower frequency and was not observed in barrel racing or racing QHs. Knowing that reining and working cow QHs have the highest prevalence of the E321G MYH1 variant and that the variant is more prevalent than the alleles for hereditary equine regional dermal asthenia and hyperkalemic periodic paralysis in the general QH population will guide the use of genetic testing for diagnostic and breeding purposes."

Albuquerque et al. (2022) “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. … 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.”

Genetic testing: Finno et al. (2018) concluded that their "results suggest that rather than consistently causing a myopathy, homozygosity and, in some cases, heterozygosity for the MYH1 variant predisposed horses to a myopathy under certain environmental triggers." In other words, the jury is still undecided in relation to the utility of genotyping for this variant as a means of selecting against the disorder.

Breed: Quarter Horse (Horse) (VBO_0001057).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: