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The Fat Controllers: Dairy Cattle Genetics and Milk Fat Composition

    Written by: Peter Williamson, Ph.D. | Issue # 38 | 2015

    • Milk fat is made up of over 400 components—each with different effects on health and dairy food value.
    • Different breeds of cows produce different amounts of the healthier components.
    • The ability of a cow to balance the composition of milk fats in her milk is influenced by her genes.
    • By combining selective breeding with specific diets, cows could produce healthier milk that is also better for making dairy foods.

    Milk is rich in each of the major nutrients: proteins, fats, and carbohydrates. We can easily recognize that milk contains fat from the cream that separates from milk and from butter and cheeses, which are rich in milk fats. But did you know that milk fat actually contains over 400 individual types of fat? These lipids (the technical term for fats) provide the fundamental ingredients that determine, for example, the cheese-making qualities and the taste and flavor. However, consumption of fats needs to be balanced in our diet so that they don’t adversely affect our health. The current consensus amongst nutritionists is that too much fat in the diet is unhealthy, and that the type of fats or fatty acids that are consumed makes a big difference. Taking all of these factors into consideration, dairy scientists from the Netherlands and Denmark have been studying the genetic basis of milk fat composition.

    Overall, fats can be divided into saturated and unsaturated categories. Nutritionists advocate that we eat less saturated fats, and increase the relative amount of unsaturated fats. The American Heart Association recommends that saturated fat should be no more than 7% of our total energy intake [1]. Although the role that dietary fats play in our health and wellbeing is not entirely clear, this recommendation has a marked effect on milk consumption. Milk fat is, on average, about 70% saturated fat, but the dairy industry has, for many years, produced a huge range of low fat dairy products through manufacturing processes. What the scientists wanted to know was, could the cows themselves produce milk with a healthier combination of fats?

    The mixture of fats in milk fat varies a lot between dairy cow breeds, different farms, and even individual cows. Depending on what the cows eat and how long they have been milking, the percentage of fat in the milk will fluctuate. Furthermore, we also know that there is a very strong genetic influence on the quantity of milk fat [2]. The Dutch, and more recently, the Danish dairy scientists, decided to dissect the milk fat into individual components, and measure the impact of the cow’s genetic makeup on each component.

    Led by Johann van Arendonk at Wageningen University, and supported through the Dutch Milk Genomics Initiative, the scientists began to collect data about ten years ago in collaboration with dairy farmers from across the Netherlands. They first set out to analyze the differences between farms, herds, and other factors that affect the composition of milk fat. Prior studies by dairy geneticists in 2002 identified a gene that codes for a naturally occurring enzyme found in cows, referred to as DGAT1, as a major determinant of milk fat percentage [3]. When van Arendonk’s graduate student, Anke Schennink began the analysis, she found that, just like the percentage of milk fat, milk fat composition was indeed influenced by the genetic background of cows. In this initial study, Schennink et al., identified a number of genomic regions associated with either short, medium, or long-chain fatty acid content in milk [4]. In further analysis, they discovered that different genetic variants of DGAT1 affected the amount of specific fatty acids in the milk fat. Indeed, the DGAT1 accounted for about half of the fat composition attributed to genetic variation that was present in the animals studied. Schennink then went further to look at the amount of unsaturated fat in the milk. They again found a large effect of the DGAT1 gene, and another lipid enzyme gene, SCD1, on unsaturated fatty acids. This success led them to extend their analysis to other prominent enzymes that synthesize or process fats. They found that specific mutations in some of these enzymes influenced the mix of fats in the milk [5,6].

    Over the past ten years, there has been a lot of excitement amongst scientists about the development of genomic technologies for studying dairy genetics. The Dutch brought these new technologies into their dairy program to expand their search for stretches of dairy cow DNA that carry genes that influence milk fat composition, but which had not been previously identified. They identified four regions from amongst many thousands analyzed, that affected the composition of fats that are mostly made in the mammary gland [7], and an additional three regions that influenced the fats that mostly get into the milk via the diet [8]. When they took a closer look at the DNA using informatics (computer-based analysis of database information), they found a number of genes that are clearly involved in fat metabolism. The technologies continued to develop, permitting an ever-increasing sensitivity for finding mutations that cause the differences in fat composition. All up, 11 genes were candidates for causing the differences in milk fat composition [9]. Additionally, they found a novel effect from a mutation in DGAT1 and, for the first time, an effect from a gene called PGRMC2 [10].

    Milk fat composition can change significantly between winter and summer, especially in regions where food sources for the cows depend on the seasons. When winter and summer milk fat compositions were compared by the Dutch scientists, there were clear differences in milk fats, but no substantial differences in how this was affected by the cow’s genetic makeup [11,12]

    Meanwhile, scientists from the Danish-Swedish Milk Genomics Initiative completed a study of milk fat composition in Danish Holsteins and also introduced a comparative analysis of the Danish Jersey breed [13]. The milk of Jersey cows is richer in fats compared to many other dairy breeds. Like the Dutch program, they were looking for genetic factors that influenced the healthier milk fats and that also controlled cheese-making qualities. They found similar effects of DGAT1 and SCD1 to add to the mounting evidence that these enzymes have the greatest influence on the type of fat found in milk. Furthermore, they also found some evidence for a new candidate gene called ACSS3 [14]. When they put all the regions together and analyzed them, they could discern a pattern of those genes that regulated fat digestion and absorption, and which had the most significant influence.

    Thanks to these enormously detailed and seminal studies, we can say that, by combining specific types of diets for the cows, and by selecting cows for breeding based on their milk fat composition, milk could become a healthier choice for consumers, and top quality for producing dairy products at the same time.

    References

    1. Lichtenstein A, Appel L, Brands M, Carnethon M, Daniels S, et al. (2006) Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. . Circulation 114: 82-96.
    2. Khatkar MS, Thomson PC, Tammen I, Raadsma HW (2004) Quantitative trait loci mapping in dairy cattle: Review and meta-analysis. . Genet Sel Evol 36: 163–190.
    3. Grisart B, Coppieters W, Farnir F, Karim L, Ford C, et al. (2002) Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res 12: 222-231.
    4. Schennink A, Stoop WM, Visker MH, Heck JM, Bovenhuis H, et al. (2007) DGAT1 underlies large genetic variation in milk-fat composition of dairy cows. Anim Genet 38: 467-473.
    5. Schennink A, Heck JM, Bovenhuis H, Visker MH, van Valenberg HJ, et al. (2008) Milk fatty acid unsaturation: genetic parameters and effects of stearoyl-CoA desaturase (SCD1) and acyl CoA: diacylglycerol acyltransferase 1 (DGAT1). J Dairy Sci 91: 2135-2143.
    6. Schennink A, Bovenhuis H, Leon-Kloosterziel KM, van Arendonk JA, Visker MH (2009) Effect of polymorphisms in the FASN, OLR1, PPARGC1A, PRL and STAT5A genes on bovine milk-fat composition. Anim Genet 40: 909-916.
    7. Stoop WM, Schennink A, Visker MH, Mullaart E, van Arendonk JA, et al. (2009) Genome-wide scan for bovine milk-fat composition. I. Quantitative trait loci for short- and medium-chain fatty acids. J Dairy Sci 92: 4664-4675.
    8. Schennink A, Stoop WM, Visker MH, van der Poel JJ, Bovenhuis H, et al. (2009) Short communication: Genome-wide scan for bovine milk-fat composition. II. Quantitative trait loci for long-chain fatty acids. J Dairy Sci 92: 4676-4682.
    9. Bouwman AC, Bovenhuis H, Visker MH, van Arendonk JA (2011) Genome-wide association of milk fatty acids in Dutch dairy cattle. BMC Genet 12: 43.
    10. Duchemin SI, Visker MH, Van Arendonk JA, Bovenhuis H (2014) A quantitative trait locus on Bos taurus autosome 17 explains a large proportion of the genetic variation in de novo synthesized milk fatty acids. J Dairy Sci 97: 7276-7285.
    11. Bouwman AC, Visker MH, van Arendonk JA, Bovenhuis H (2012) Genomic regions associated with bovine milk fatty acids in both summer and winter milk samples. BMC Genet 13: 93.
    12. Duchemin S, Bovenhuis H, Stoop WM, Bouwman AC, van Arendonk JA, et al. (2013) Genetic correlation between composition of bovine milk fat in winter and summer, and DGAT1 and SCD1 by season interactions. J Dairy Sci 96: 592-604.
    13. Krag K (2013) Genetic parameters for milk fatty acids in Danish Holstein cattle based on SNP markers using a Bayesian approach BMC Genetics 14: 79-89.
    14. Buitenhuis B (2014) Genome-wide association and biological pathway analysis for milk-fat composition in Danish Holstein and Danish Jersey cattle. BMC Genomics 15: 1112-1123.