Genetic regulators of mineral amount in Nelore cattle muscle predicted by a new co-expression and regulatory impact factor approach

Abstract

Mineral contents in bovine muscle can affect meat quality, growth, health, and reproductive traits. to better understand the genetic basis of this phenotype in nelore (Bos indicus) cattle, we analysed genome-wide mRNA and miRNA expression data from 114 muscle samples. The analysis implemented a new application for two complementary algorithms: the partial correlation and information theory (pcit) and the regulatory impact factor (Rif), in which we included the estimated genomic breeding values (GeBVs) for the phenotypes additionally to the expression levels, originally proposed for these methods. We used PCIT to determine putative regulatory relationships based on significant associations between gene expression and GeBVs for each mineral amount. then, Rif was adopted to determine the regulatory impact of genes and miRnAs expression over the GeBVs for the mineral amounts. We also investigated over-represented pathways, as well as pieces of evidences from previous studies carried in the same population and in the literature, to determine regulatory genes for the mineral amounts. for example, NOX1 expression level was positively correlated to Zinc and has been described as Zinc-regulated in humans. Based on our approach, we were able to identify genes, miRnAs and pathways not yet described as underlying mineral amount. the results support the hypothesis that extracellular matrix interactions are the core regulator of mineral amount in muscle cells. putative regulators described here add information to this hypothesis, expanding the knowledge on molecular relationships between gene expression and minerals. Besides nutritional quality, mineral amount affects meat quality in many ways. For example, the tenderization process of the skeletal muscle is driven by the action of the calcium-dependent protease calpain 1-4. Minerals also affect reproduction, as copper, zinc, selenium and manganese supplementation improves pregnancy rate 5 ; as well as health and growth performance 6,7 in beef cattle. Mineral homeostasis regulation partially depends on genetic factors, among others 8. Thus, understanding the genetic aspects linked to mineral amount in bovine muscle can

Repressive epigenetic mechanisms, such as the H3K27me3 histone modification, were predicted to affect muscle gene expression and its mineral content in Nelore cattle

“…The genes SIM2, COMP, HOXC10, HOXC4, LMX1B, RBFOX3, CRTAC1, ZIC4, CDH22 and SIM1 , had a high position in both ranks from each contrasting group (marked in bold in Supplementary Tables S2–S21 and Table 2 ). Table 2 shows a list of DRGs for each mineral comparison that are also differentially expressed genes (DEGs) [ 5 , 7 ], genes with expression correlated to the specific mineral mass fraction and genes presenting a regulatory impact over the same specific mineral mass fraction (RIF) [ 8 ] and the other attributes for these genes, does showing that they were already linked to mineral content in our population. Supplementary Fig.…”

“…Minerals are often components of metalloenzymes and act as enzymatic cofactors, involved in protection against oxidative stress, and being relevant to muscle metabolism, hormone synthesis, and protein bonds [ 3 ]. Previous work identified genes and genomic regions of relevance to the mineral content of muscle cells in Nelore cattle [ [4] , [5] , [6] , [7] , [8] ]. However, the mechanisms regulating the expression of these genes are not fully understood.…”

Genomic analyses of claw disorders in Holstein cows: Genetic parameters, trait associations, and genome-wide associations considering interactions of SNP and heat stress

“…The potential candidate gene UBQLN1 on BTA 8 influences protein degradation in vivo, and proteins interacted with diseases such as the foot and mouth disease virus (Gladue et al, 2014). The potential candidate gene WDPCP on BTA 11 plays a crucial role in collective cell movement and cilia formation, explaining the involvement in disease resistance mechanisms (e.g., de las Heras-Saldana et al, 2019;Afonso et al, 2020). The potential candidate gene ITPR1 on BTA 22 encodes an intracellular receptor for inositol-1, 4, 5-triphosphate, and was active in the presence of external stressors (Cheruiyot et al, 2021).…”

Nutrigenomics in livestock: potential role in physiological regulation and practical applications

“…PCIT) (Reverter and Chan 2008) also has allowed for identifying significant gene-togene associations within a tissue and among tissues. This approach has been used to study regulatory mechanisms controlling phenotypes that can be affected by nutrition, such as marbling (Cesar et al 2015(Cesar et al , 2018 or the mineral content of meat (Afonso et al 2020). Besides ChEA3, identification of biologically relevant TF and target-gene networks can be conducted through implementation of regulatory impact factor (RIF) algorithms (Reverter et al 2010).…”