Integrative Whole-Genome Analysis reveals Genomic Signatures of Innate Immunity in Indicine Cattle

Indicine cattle ( Bos indicus ) are known for resilience to infectious diseases and environmental stress. However, the genomic basis underlying this advantage remains poorly understood. To characterize variations in immune-related genetic elements in four indicine breeds (Kangayam, Gir, Tharparkar, and Sahiwal), a taurine breed (Holstein Friesian), and a taurine–indicine crossbreed (Karan Fries), we performed integrative whole-genome analysis. Using whole-genome data representing 108 animals, we identified structural variants, copy number variants, single-nucleotide variations, and insertions/deletions. High-impact single-nucleotide variations in the key innate immune genes, CARD9 and NLRP8 , shared across all indicine breeds, were absent in the other breeds. Genetic differentiation analysis identified several innate immune genes showing strong divergence between the indicine breeds and the taurine breed. Selective sweep detection analysis highlighted multiple breed-specific immune-related sweep regions. Functional enrichment analysis showed significant enrichment of immune pathways in indicine breeds. A comparison of the candidate genes with basal gene expression profiles of unchallenged peripheral blood mononuclear cells indicated that genomic variation influences the differential expression of several genes in indicine breeds. We synthesized the data from population genome structure analysis, nucleotide diversity, genetic differentiation, selective sweep analysis, and correlations with gene expression profiles. Indicine breeds exhibited a higher number of immune-related variants and stronger signals of selection in immune pathways. These findings provide a curated set of innate immune gene candidates in indicine breeds for future functional studies and breeding programs.