Integrative population genomics and tissue-specific expression profiling in cattle using whole-genome sequence resources

Large-scale genomic resources enable systematic investigation of genetic variation and tissue-specific expression of immune-related pathways in livestock species. Here, we integrated population-level whole-genome sequence data with tissue-specific transcriptional profiling to characterize genomic differentiation and expression patterns of NF-κB pathway-related genes in cattle. Using whole-genome sequence data from the 1000 Bull Genomes Project, we identified prioritized differentiated variants within several NF-κB pathway-related genes, including CD14, NF-κB1, IL-1β, and BAFFR. The mRNA expression levels of selected NF-κB signaling-related genes were quantified across four tissues with relevance to host defense and metabolism in bulls and cows of both breeds. Expression analyses revealed pronounced tissue-dependent regulation, with distinct organ-specific transcriptional patterns across the investigated genes. Intestinal tissues showed lower expression of several innate immune genes, whereas CD14 expression was more prominent in liver-associated comparisons, highlighting functional tissue specialization within the NF-κB signaling network. Breed- and sex-associated effects were gene-dependent rather than uniform across the pathway. Histological assessment of the spleen was performed to provide an anatomical context for observed transcriptional variations. A population-prioritized CD14 missense variant (Asn177Asp), identified from the 1000 Bull Genomes dataset, was contextualized using in silico structural annotation to provide structural context for coding variation. These findings provide descriptive evidence that population-level genomic differentiation in selected NF-κB pathway genes is accompanied by tissue-specific transcriptional differences in cattle.