Genetic polymorphism of caseins: a tool to investigate casein micelle organization

Abstract

Abstract The unusual and complex polymorphism, detected at the α s1 -Cas locus has been shown to be partly responsible for the large individual variability observed in the casein content of goat milk, and for its poor clotting ability. Structural analyses performed at the protein and subsequently at the nucleotide levels have provided an understanding of the molecular basis of this genetic polymorphism and prompted the speculation that it might be exploited to improve, through selection, cheese-making properties of goat milk. So far, at least 13 alleles have been described at this locus. They are distributed into seven different classes of protein variants ( α s1 -CasA to α s1 -CasG) of which some appear to be internally deleted, associated with four levels of expression ranging between 0 ( α s1 -CasO) and 3.5 g/l ( α s1 -CasA, B and C), per allele. The large deletion (37 amino acid residues) occurring within variant F removes a highly hydrophilic part of the molecule including a cluster of five phosphoseryl residues involved in interactions, through colloidal calcium phosphate, between submicelle units. Such an event is not without any effect on the organization and the physico-chemical properties of the micelle, particularly in terms of size and calcium content. Mutations responsible for this genetic polymorphism have been identified, thus having allowed the development of genotyping procedures based on the polymerase chain reaction technique. Morphological observations performed at the cellular level, on mammary tissue sections have revealed that goats homozygous for the defective alleles ( α s1 -CasE, F, G and O) display epithelial cells with a dramatic swelling of the rough endoplasmic reticulum primarily due to an accumulation of proteins, that strongly suggests a dysfunction in secretion mechanisms. A defective allele has been also found, in the goat, at the β -casein locus ( β -CasO) which makes this species, with its highly polymorphic casein system, a valuable and unique tool to investigate casein micelle organization.