Objectives: Genome-wide association studies (GWAS) represent a powerful approach to detecting candidate genes for economically important traits in livestock. Our aim was to identify promising candidate muscle development genes that affect net meat weight (NMW) and validate these candidate genes in cattle.
Materials and methods: Using a next-generation sequencing (NGS) dataset, we applied ~ 12 million imputed single nucleotide polymorphisms (SNPs) from 1,252 Simmental cattle to detect genes influencing net meat yield by way of a linear mixed model method. Haplotype and linkage disequilibrium (LD) blocks were employed to augment support for identified genes. To investigate the role of MTPN in bovine muscle development, we isolated myoblasts from the longissimus dorsi of a bovine foetus and treated the cells during proliferation, differentiation and hypertrophy.
Results: We identified one SNP (rs100670823) that exceeded our stringent significance threshold (P = 8.58 × 10-8 ) for a putative NMW-related quantitative trait locus (QTL). We identified a promising candidate gene, myotrophin (MTPN), in the region around this SNP Myotrophin had a stimulatory effect on six muscle-related markers that regulate differentiation and myoblast fusion. During hypertrophy, myotrophin promoted myotube hypertrophy and increased myotube diameters. Cell viability assay and flow cytometry showed that myotrophin inhibited myoblast proliferation.
Conclusions: The present experiments showed that myotrophin increases differentiation and hypertrophy of skeletal muscle cells, while inhibiting their proliferation. Our examination of GWAS results with in vitro biological studies provides new information regarding the potential application of myotrophin to increase meat yields in cattle and helpful information for further studies.
Keywords: Differentiation; GWAS; NGS; NMW; Proliferation.
© 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.