Prediction of hub genes associated with intramuscular fat content in Nelore cattle

The aim of this study was to use transcriptome RNA-Seq data from longissimus thoracis muscle of uncastrated Nelore males to identify hub genes based on co-expression network obtained from differentially expressed genes (DEGs) associated with intramuscular fat content. A total of 30 transcriptomics datasets (RNA-Seq) obtained from longissimus thoracis muscle were selected based on the phenotypic value of divergent intramuscular fat content: 15 with the highest intramuscular fat content (HIF) and 15 with the lowest intramuscular fat content (LIF). The transcriptomics datasets were aligned with a reference genome and 65 differentially expressed genes (DEGs) were identified, including 21 upregulated and 44 downregulated genes in HIF animals. The normalized count data from DEGs was then used for co-expression network construction. From the co-expression network, four modules were identified. The topological properties of the network were analyzed; those genes engaging in the most interactions (maximal clique centrality method) with other DEGs were predicted to be hub genes (PDE4D, KLHL30 and IL1RAP), which consequently may play a role in cellular and/or systemic lipid biology in Nelore cattle. Top modules screened from the gene co-expression network were identify. The two candidate modules had clear associated biological pathways related to fat development, cell adhesion, and muscle differentiation, immune system, among others. The hub genes belonged in top modules and were downregulated in HIF animals. PDE4D and IL1RAP have known effects on lipid metabolism and the immune system through the regulation of cAMP signaling. Given that cAMP is known to play a role in lipid systems, PDE4D and IL1RAP downregulation may contribute to increased levels of intracellular cAMP and thus may have effects on IF content differences in Nelore cattle. KLHL30 may have effects on muscle metabolism. Klhl protein families play a role in protein degradation. However, the downregulation of this gene and its role in lipid metabolism has not yet been clarified. The results reported in this study indicate candidate genes and molecular mechanisms involved in IF content difference in Nelore cattle.