Abstract
The quantities and proportions of protein fractions have notable effects on the nutritional and technological value of milk. Although much is known about the effects of genetic variants on milk proteins, the complex relationships among the set of genes and pathways regulating the different protein fractions synthesis and secretion into milk in dairy cows are still not completely understood. We conducted genome-wide association studies (GWAS) for milk nitrogen fractions in a cohort of 1,011 Brown Swiss cows, which uncovered 170 significant single nucleotide polymorphism (SNPs), mostly located on BTA6 and BTA11. Gene-set analysis and the network-based Associated Weight Matrix approach revealed that the milk proteins associated genes were involved in several biological functions, particularly ion and cation transmembrane transporter activity and neuronal and hormone signalling, according to the structure and function of casein micelles. Deeper analysis of the transcription factors and their predicted target genes within the network revealed that GFI1B, ZNF407 and NR5A1 might act as master regulators of milk protein synthesis and secretion. The information acquired provides novel insight into the regulatory mechanisms controlling milk protein synthesis and secretion in bovine mammary gland and may be useful in breeding programmes aimed at improving milk nutritional and/or technological properties.
Highlights
Milk is an important source of proteins of high-quality due to their high content of essential amino acids, such as lysine, which is deficient in many human diets[1], and their well-known physiological effects, such as immunomodulatory and gastrointestinal activities[2]
Milk payment systems in the dairy sectors producing hard cheeses with EU Protected Designation of Origin (PDO) status often include among their payment criteria coagulation and curd firming properties, which are strongly affected by the amounts, proportions and genetic variants of milk protein fractions[8], as these are related to cheese quality and sensory properties[9,10]
It has been shown that CN phosphorylation, one of the most important factors controlling the stabilization of calcium phosphate nanoclusters in casein micelles and the internal structure of the casein micelles[15], is essential for the protein synthesis machinery in the mammary gland
Summary
Milk is an important source of proteins of high-quality due to their high content of essential amino acids, such as lysine, which is deficient in many human diets[1], and their well-known physiological effects, such as immunomodulatory and gastrointestinal activities[2]. The other protein category is the whey proteins fraction, which consists of mainly β-lactoglobulin (β-LG) and α-lactalbumin (α-LA), immunoglobulins, serum albumin, lactoferrin, lactoperoxidase and a minor component corresponding to glycomacropeptide[3] This fraction make up approximately 20% of total milk proteins[4] and it is demonstrated to affect satiety by reducing food intake, stimulating satiating gut hormone production and slowing stomach emptying in humans and animal models (reviewed by Sánchez-Moya et al.[5]). There have been extraordinary advances in our knowledge of the physiology and biochemistry of the lactating mammary gland Despite such efforts, little is as yet known of the genetic regulation of the physiological and cellular mechanisms required for milk protein synthesis and secretion. Deeper knowledge of the set of genes and pathways regulating bovine milk protein synthesis and secretion might, help to identify their contribution to optimising casein and whey protein contents during lactation. Pathway-based and gene network analyses have been often used as complementary approaches for extracting biological information from genome-wide association analysis studies (GWAS) and for better characterising the genomic structure of complex traits[21,22]
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