The 6 main milk proteins in cattle are encoded by highly polymorphic genes characterized by several nonsynonymous and synonymous mutations, with up to 47 protein variants identified. Such an extensive variation was used for linkage analysis with the description of the casein cluster more than 30 yr ago and has been applied to animal breeding for several years. Casein haplotype effects on productive traits have been investigated considering information on the whole casein complex. Moreover, mutations within the noncoding sequences have been shown to affect the specific protein expression and, as a consequence, milk composition and cheesemaking. Milk protein variants are also a useful tool for breed characterization, diversity, and phylogenetic studies. In addition, they are involved in various aspects of human nutrition. First, the occurrence of alleles associated with a reduced content of different caseins might be exploited for the production of milk with particular nutritional qualities; that is, hypoallergenic milk. On the other hand, the frequency of these alleles can be decreased by selection of sires using simple DNA tests, thereby increasing the casein content in milk used for cheesemaking. Furthermore, the biological activity of peptides released from milk protein digestion can be affected by amino acid exchanges or deletions resulting from gene mutations. Finally, the gene-culture coevolution between cattle milk protein genes and human lactase genes, which has been recently highlighted, is impressive proof of the nonrandom occurrence of milk protein genetic variation over the centuries.

The aim of this review was to focus on the complex relationships between milk and dairy products intake and bone health, with particular emphasis on osteoporosis. The literature was extensively examined to provide an objective overview of the most significant achievements on the subject. Osteoporosis can be defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Although the major determinants of peak bone mass and strength are genetic, major factors during childhood and adolescence may affect the ability to achieve peak bone mass. These include nutrition, particularly calcium and protein intake, physical activity, endocrine status, as well as exposure to a wide variety of risk factors. The role of calcium intake in determining bone mineral mass is well recognized to be the most critical nutritional factor to achieve optimal peak bone mass. The greatest amount of dietary calcium is obtained from milk and dairy foods, which also provide the human diet with vitamin D (particularly for products fortified with vitamin D), potassium, and other macro- and micronutrients. Although studies supporting the beneficial effects of milk or calcium on bone health are predominant in the literature, perplexity or discordance on this subject was expressed by some authors. Discordant data, mainly on the risk of fractures, provided limited proof of the unfavorable effect of dairy intake. More often, discordant works indicate no effect of dairy consumption on bone safety. Some considerations can be drawn from this viewpoint. Milk and dairy products are an optimal source of calcium as well as of other limiting nutrients (e.g., potassium and magnesium), with important effects on bone health. Bioactive components occurring in milk and dairy products may play an essential role on bone metabolism, as shown by in vivo and in vitro studies on colostrum acidic proteins and milk basic proteins. Calcium intake positively affects bone mass and is crucial in childhood and youth for correct bone development. In elderly people, calcium intake as well as vitamin D availability should be carefully checked. As a general conclusion, calcium is essential for bone health, although it will not prevent bone loss due to other factors; in this context, milk and dairy foods are bioavailable, relatively inexpensive sources of calcium for the human diet.

Cow milk allergy is the most frequent allergy in the first years of life. Milk from other mammalian species has been suggested as a possible nutritional alternative to cow milk, but in several cases, the clinical studies showed a high risk of cross-reactivity with cow milk. In the goat species, αS₁-casein (αS₁-CN), coded by the CSN1S1 gene, is characterized by extensive qualitative and quantitative polymorphisms. Some alleles are associated with null (i.e., CSN1S1 0(1)) or reduced (i.e., CSN1S1 F) expression of the specific protein. The aim of this work was to obtain new information on goat milk and to evaluate its suitability for allergic subjects, depending on the genetic variation at αs₁-CN. Individual milk samples from 25 goats with different CSN1S1 genotypes were analyzed by sodium dodecyl sulfate PAGE and immunoblotting, using monoclonal antibodies specific for bovine α-CN and sera from children allergic to cow milk. A lower reaction was observed to 2 goat milk samples characterized by the CSN1S1 0(1)0(1) and 0(1)F genotypes. Moreover, a fresh food skin prick test, carried out on 6 allergic children, showed the lack of positive reaction to the 0(1)0(1) milk sample and only one weak reactivity to the 0(1)F sample. The risk of cross-reactivity between cow and goat milk proteins suggests the need for caution before using goat milk for infant formulas. However, we hypothesize that it can be used successfully in the preparation of modified formulas for selected groups of allergic patients. The importance of taking the individual goat CN genetic variation into account in further experimental studies is evident from the results of the present work.

The analysis of casein polymorphisms was carried out in West Africa goat populations: Red Sokoto (n = 57), West African Dwarf Nigeria (n = 27), West African Dwarf Cameroon (n = 39), and Borno (n = 37). The 4 casein genes alpha(s1) (CSN1S1), beta (CSN2), alpha(s2) (CSN1S2), and kappa (CSN3) were typed at the DNA level. No null alleles were found in any of the genes analyzed. A PCR single-strand conformation polymorphism method was implemented for the identification of CSN1S1*F allele simultaneously with A/0(1), B/E, N and the new allele. The allele differed from CSN1S1*B by a synonymous transversion TCG-->TCT in the codon corresponding to Ser(66) of the mature protein. The new allele, named CSN1S1*B', occurred at a high frequency in all the populations, ranging from 0.295 (West African Dwarf Cameroon) to 0.405 (Borno). A greater frequency was found for alleles associated with high alpha(s1)-casein quantity, as has already been observed in the goat populations from the Mediterranean area. The intermediate E allele occurred only in the Red Sokoto and at a low frequency. The faint F allele occurred in 3 populations at frequencies lower than 0.03. Linkage disequilibrium occurred in all the populations, with highly significant differences in Borno, Red Sokoto, and West Africa Dwarf Nigeria, and significant differences in West Africa Dwarf Cameroon. Only 10 haplotypes showed frequencies > or =0.05 in at least 1 of the 4 populations considered, and the overall frequency was >0.1 only for 4 haplotypes: BAAB, B'ACA, ACAB, and BACA (in the order CSN1S1-CSN2-CSN1S2-CSN3). Haplotype BAAB, postulated as an ancestral haplotype in previous studies, was the most common haplotype in all breeds except Borno, where B'ACA was predominant. The results obtained are of considerable significance given that very little information exists on the subject for African goats. The high frequency of strong alleles in the calcium-sensitive caseins as well as the high linkage disequilibrium found among the casein genes in the African breeds analyzed may suggest that specific casein haplotypes have already been selected due to their advantages for nutrition. Haplotypes providing greater protein and casein content would increase the energy content of milk, thus resulting in more favorable growth and survival of young goats and humans consuming the milk.

The aim of this work was to study the effects of isoelectrofocusing (IEF) milk protein variants on milk composition in the Italian Orobica goat breed, which is characterized by a rather high frequency of the kappa-casein (CSN3) B(IEF) allele. Significant associations were found between the IEF phenotype and protein and casein percentages. A favorable effect of the CSN3 B(IEF) variant was found for both protein and casein percentages, with a codominance trend for the 3 phenotypes: BB > AB > AA. Depending on the selection purpose, emphasis could be given to different kappa-casein variants in breeding. The high frequency of B(IEF) could be exploited in breeding strategies to improve the protein and casein percentages when cheese making is a selection objective.