Global analysis of bovine milk protein variants using multi-breed DNA sequence data.

backgroundTo date, 63 variants of six major bovine milk proteins (α

resultsWe investigated variants of the six major milk proteins in 3,824 cattle representing 113 breeds with wide geographical distribution using whole genome sequencing data. 59 missense variants of milk protein genes that can alter the amino acid sequence of the mature protein were detected. Notably, 10 out of 11 missense variants in CSN3 were located within the region coding for the glyco-macropeptide, whereas the para-κ-casein region involved in micelle stabilization remained highly conserved with only one variant detected, suggesting functional constraint in this region. A total of 121 milk protein variants were identified based on different combinations of the 59 missense variants, of which 35 had been described previously. We detected 86 novel variants that had not been reported previously. These protein variants were likely missed in earlier studies due to technical limitations or the use of limited number of animals or breeds.

conclusionThis study provides a comprehensive overview of milk protein diversity across global cattle breeds, offering valuable insights for improving milk quality and properties, guiding selective breeding and prioritizing variants for future functional investigation in the dairy sector.