Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy

• Published in: Equine veterinary journal 2021-03, Vol.53 (2), p.306-315
• Main Authors: Williams, Zoë J., Velez‐Irizarry, Deborah, Petersen, Jessica L., Ochala, Julien, Finno, Carrie J., Valberg, Stephanie J.
• Format: Article
• Language: English
• Subjects: Animals; Case-Control Studies; contractility; Female; Gene Expression; horse; Horse Diseases - genetics; Horses - genetics; Male; Muscle, Skeletal; Myopathies, Structural, Congenital - genetics; Myopathies, Structural, Congenital - veterinary; myopathy; RNAseq; skeletal muscle
• ISSN: 0425-1644; 2042-3306; 2042-3306
• DOI: 10.1111/evj.13286

Background Myofibrillar myopathy (MFM) of unknown aetiology has recently been identified in Warmblood (WB) horses. In humans, 16 genes have been implicated in various MFM‐like disorders. Objectives To identify variants in 16 MFM candidate genes and compare allele frequencies of all variants between MFM WB and non‐MFM WB and coding variants with moderate or severe predicted effects in MFM WB with publicly available data of other breeds. To compare differential gene expression and muscle fibre contractile force between MFM and non‐MFM WB. Study design Case‐control. Animals 8 MFM WB, 8 non‐MFM WB, 33 other WB, 32 Thoroughbreds, 80 Quarter Horses and 77 horses of other breeds in public databases. Methods Variants were called within transcripts of 16 candidate genes using gluteal muscle mRNA sequences aligned to EquCab3.0 and allele frequencies compared by Fisher's exact test among MFM WB, non‐MFM WB and public sequences across breeds. Candidate gene differential expression was determined between MFM and non‐MFM WB by fitting a negative binomial generalised log‐linear model per gene (false discovery rate