PSII-6 Genomic association study and metabolic pathway enrichment for the validation of molecular markers and genes associated with meat tenderness in Nellore cattle.

Abstract Identifying and selecting animals with high potential for producing tender meat is essential for enhancing the efficiency and competitiveness of Brazilian livestock. This study aimed to conduct weighted single-step genome-wide association analyses (WssGWAS) to identify and validate genomic regions, genes, and metabolic pathways associated with meat tenderness in Nellore cattle. Two datasets were analyzed: (1) a complete dataset (n=1,164), including genotyped animals with or without phenotypic records but with progeny, animals with phenotypic records but not genotyped, and genotyped animals with phenotypic records but lacking progeny details. These animals were born between 2002 and 2022 and were slaughtered at an average age of 25.55±3.90 months. A partial dataset (n=374), consisting of young, genotyped animals without progeny records, where phenotypic information was not included. These animals were born between 2021 and 2022. The correlation between SNP effect estimates in each dataset was 0.29. After performing genomic quality control, the final dataset included 15,299 animals and 58,734 SNPs. Genomic regions explaining more than 0.5% of the additive genetic variance for met tenderness were considered potential quantitative trait loci (QTLs). Gene classification related to biological functions, metabolic pathways, and pathway enrichment was conducted using the DAVID tool, with a significance threshold set at a P-value < 0.05. Considering the complete and partial dataset, markers, regions, and genes identified in this analysis were compared to validate the markers identified in the first WssGWAS study. Across populations, seven genomic regions (chromosomes 3, 5, 7, 9, 18, 20, and 24) showed consistent associations, indicating robust links across generations. In total, 37 genes were found to be enriched for meat tenderness in overlapping pathways when evaluating both complete and partial populations. Notably, these included members of the olfactory receptor family, genes from the SERPINB family, genes related to cell signaling (ADGR1 and ADGR3), genes associated with remodeling and mechanical response (KLF2), extracellular matrix degradation (MMP2), and actin-myosin interaction regulation (TPM4). Five Gene Ontology (GO) terms exhibited statistically significant gene associations with meat tenderness across both the complete and partial populations. Among these, two belonged to the molecular function domain (MF): olfactory receptor activity (GO:0004984) and G protein-coupled receptor activity (GO:0004930). The remaining three terms were related to the biological process domain (BP): negative regulation of endopeptidase activity (GO:0010951), sensory perception of smell (GO:0007608), and G protein-coupled receptor signaling pathway (GO:0007186). Additionally, one KEGG pathway, Olfactory transduction (bta04740), was statistically significant in both populations. These findings offer valuable insights into the genetic basis of meat tenderness and support the potential use of genomic selection to enhance this trait in Nellore cattle.