Integrative multi-omics analysis identifies C-type lectin CNVs as functional targets for breeding mastitis-resistant dairy goats

Mastitis poses a critical challenge to dairy goat production, impacting animal welfare, milk yield, and the microbiological safety of dairy products. This study employed a multi-omics approach to explore the genetic basis of mastitis resistance in Saanen goats, focusing on identifying functional copy number variants (CNVs) and their roles in immune regulation. A genome-wide scan identified 62,860 CNVs, with 115 exhibiting strong selection signals. Among these, two adjacent CNVs overlapping with the C-type lectin genes LOC108636060 and LOC108636138 were noteworthy due to their high deletion frequencies in the population of Saanen goats. Functional investigations involving lipopolysaccharide (LPS)-challenged goat mammary epithelial cells (GMECs) demonstrated that the overexpression of these two C-type lectin genes significantly potentiated NF-κB signaling pathway activation. This was accompanied by the marked upregulation of key inflammatory mediators, including CD14, CXCL8, and PTGS2. Integrated metabolomic analysis further validated their involvement in modulating immune-associated metabolic responses, such as alterations in lipid metabolism, amino acid derivatives, and inflammatory signaling molecules. These findings indicate that LOC108636060 and LOC108636138 could contribute to mastitis resistance through the regulation of innate immune pathways, with critical roles in orchestrating inflammatory responses. Their functional relevance suggests these genes may serve as promising candidates for selective breeding programs. Incorporating these markers into breeding strategies could facilitate the improvement of udder health, bolster mastitis resistance, and contribute to the overall safety of milk products in dairy goat production.