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A high resolution SNP map was constructed for the bovine casein region to identify haplotype structures and study associations with milk traits in Norwegian Red cattle. Our analyses suggest separation of the casein cluster into two haplotype blocks, one consisting of the  CSN1S1 ,  CSN2  and  CSN1S2  genes and another one consisting of the  CSN3  gene. Highly significant associations with both protein and milk yield were found for both single SNPs and haplotypes within the  CSN1S1-CSN2-CSN1S2  haplotype block. In contrast, no significant association was found for single SNPs or haplotypes within the  CSN3  block. Our results point towards  CSN2  and  CSN1S2  as the most likely loci harbouring the underlying causative DNA variation. In our study, the most significant results were found for the SNP  CSN2_67  with the C allele consistently associated with both higher protein and milk yields.  CSN2_67  calls a C to an A substitution at codon 67 in β-casein gene resulting in histidine replacing proline in the amino acid sequence. This polymorphism determines the protein variants A1/B ( CSN2_67  A allele) versus A2/A3 ( CSN2_67  C allele). Other studies have suggested that a high consumption of A1/B milk may affect human health by increasing the risk of diabetes and heart diseases. Altogether these results argue for an increase in the frequency of the  CSN2_67  C allele or haplotypes containing this allele in the Norwegian Red cattle population by selective breeding.

Casein haplotypes and their association with milk production traits in Norwegian Red cattle