1. Commercial genetic testing for type 2 polysaccharide storage myopathy and myofibrillar myopathy does not correspond to a histopathological diagnosis
- Author
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Valberg, Stephanie J, Finno, Carrie J, Henry, Marisa L, Schott, Melissa, Velez‐Irizarry, Deborah, Peng, Sichong, McKenzie, Erica C, and Petersen, Jessica L
- Subjects
Veterinary Sciences ,Agricultural ,Veterinary and Food Sciences ,Biological Sciences ,Genetics ,Clinical Research ,Animals ,Cross-Sectional Studies ,Genetic Testing ,Horse Diseases ,Horses ,Muscle ,Skeletal ,Myopathies ,Structural ,Congenital ,Polysaccharides ,horse ,muscle disease ,glycogen ,skeletal muscle ,validation ,Agricultural and Veterinary Sciences ,Agricultural ,veterinary and food sciences ,Biological sciences - Abstract
BackgroundCommercial genetic tests for type 2 polysaccharide storage myopathy (PSSM2) and myofibrillar myopathy (MFM) have not been validated by peer-review, and formal regulation of veterinary genetic testing is lacking.ObjectivesTo compare genotype and allele frequencies of commercial test variants (P variants) in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323), FLNC (P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) between Warmblood (WB) and Arabian (AR) horses diagnosed with PSSM2/MFM by muscle histopathology, and phenotyped breed-matched controls. To quantify variant frequency in public repositories of ancient and modern horse breeds.Study designCross sectional using archived clinical material and publicly available data.MethodsWe studied 54 control-WB, 68 PSSM2/MFM-WB, 30 control-AR, 30 PSSM2/MFM-AR and 205 public genotypes. Variants were genotyped by pyrosequencing archived DNA. Genotype and allele frequency, and number of variant alleles or loci were compared within breed between controls, PSSM2/MFM combined and MFM or PSSM2 horses considered separately using additive/genotypic and dominant models (Fisher's exact tests). Variant frequencies in modern, early domestic and Przewalski horses were determined from a public data repository.ResultsThere was no significant association between any P locus and a histopathological diagnosis of PSSM2/MFM, and no difference between control and myopathic horses in total loci with alternative alleles, or total alternate alleles when PSSM2/MFM was considered combined or separately as PSSM2 or MFM. For all tests, sensitivity was
- Published
- 2021