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Polymorphisms in genes in the SREBP1 signalling pathway and SCD are associated with milk fatty acid composition in Holstein cattle

Published online by Cambridge University Press:  25 November 2011

Gonzalo Rincon
Affiliation:
Department of Animal Science, University of California, Davis, CA 95616, USA
Alma Islas-Trejo
Affiliation:
Department of Animal Science, University of California, Davis, CA 95616, USA
Alejandro R Castillo
Affiliation:
University of California, Cooperative Extension, Merced County, CA 95341, USA
Dale E Bauman
Affiliation:
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA
Bruce J German
Affiliation:
Department of Food Science and Technology, University of California, Davis, CA 95616, USA
Juan F Medrano*
Affiliation:
Department of Animal Science, University of California, Davis, CA 95616, USA
*
*For correspondence; e-mail: jfmedrano@ucdavis.edu

Abstract

Genes in the sterol regulatory element-binding protein-1 (SREBP1) pathway play a central role in regulation of milk fat synthesis, especially the de-novo synthesis of saturated fatty acids. SCD, a SREBP-responsive gene, is the key enzyme in the synthesis of monounsaturated fatty acids in the mammary gland. In the present study, we discovered SNP in candidate genes associated with this signalling pathway and SCD to identify genetic markers that can be used for genetic and metabolically directed selection in cattle. We resequenced six candidate genes in the SREBP1 pathway (SREBP1, SCAP, INSIG1, INSIG2, MBTPS1, MBTPS2) and two genes for SCD (SCD1 and SCD5) and discovered 47 Tag SNP that were used in a marker-trait association study. Milk and blood samples were collected from Holstein cows in their 1st or 2nd parity at 100–150 days of lactation. Individual fatty acids from C4 to C20, saturated fatty acid (SFA) content, monounsaturated fatty acid content, polyunsaturated fatty acid content and desaturase indexes were measured and used to perform the asociation analysis. Polymorphisms in the SCD5 and INSIG2 genes were the most representative markers associated with SFA/unsaturated fatty acid (UFA) ratio in milk. The analysis of desaturation activity determined that markers in the SCD1 and SCD5 genes showed the most significant effects. DGAT1 K232A marker was included in the study to examine the effect of this marker on the variation of milk fatty acids in our Holstein population. The percentage of variance explained by DGAT1 in the analysis was only 6% of SFA/UFA ratio. Milk fat depression was observed in one of the dairy herds and in this particular dairy one SNP in the SREBP1 gene (rs41912290) accounted for 40% of the phenotypic variance. Our results provide detailed SNP information for key genes in the SREBP1 signalling pathway and SCD that can be used to change milk fat composition by marker-assisted breeding to meet consumer demands regarding human health, as well as furthering understanding of technological aspects of cows' milk.

Type
Research Article
Copyright
Copyright © Proprietors of Journal of Dairy Research 2011

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References

Barrett, JC, Fry, B, Maller, J & Daly, MJ 2005 Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21 263265CrossRefGoogle ScholarPubMed
Bauman, DE & Griinari, JM 2001 Regulation and nutritional manipulation of milk fat: low-fat milk syndrome. Livestock Production Science 70 1529CrossRefGoogle Scholar
Bauman, DE & Griinari, JM 2003 Nutritional regulation of milk fat synthesis. Annual Reviews of Nutrition 23 203227CrossRefGoogle ScholarPubMed
Bauman, DE, Mather, IH, Wall, RJ & Lock, AL 2006 Major advances associated with the biosynthesis of milk. Journal of Dairy Science 89 12351243CrossRefGoogle Scholar
Baumgard, LH, Matitashvili, E, Corl, BA, Dwyer, DA & Bauman, DE 2002 trans-10, cis-12 conjugated linoleic acid decreases lipogenic rates and expression of genes involved in milk lipid synthesis in dairy cows. Journal of Dairy Science 85 21552163CrossRefGoogle ScholarPubMed
Bouwman, AC, Bovenhuis, H, Visker, MH & van Arendonk, JA 2010 Genome-wide association of the ratio of saturated to unsaturated milk fatty acids in Dutch dairy cattle. In: 9th World Congress on Genetics Applied to Livestock Production (WCGALP) p. 450. Leipzig, GermanyGoogle Scholar
Bouwman, AC, Bovenhuis, H, Visker, MH & van Arendonk, JA 2011 Genome-wide association of milk fatty acids in Dutch dairy cattle. BMC Genetics 12 43CrossRefGoogle ScholarPubMed
Canovas, A, Rincon, G, Islas-Trejo, A, Wickramasinghe, S & Medrano, JF 2010 SNP discovery in the bovine milk transcriptome using RNA-Seq technology. Mammary Genome 21 592598CrossRefGoogle ScholarPubMed
Chouinard, PY, Corneau, L, Barbano, DM, Metzger, LE & Bauman, DE 1999 Conjugated linoleic acids alter milk fatty acid composition and inhibit milk fat secretion in dairy cows. Journal of Nutrition 129 15791584CrossRefGoogle ScholarPubMed
Christie, WW 1982 A simple procedure for rapid transmethylation of glycerolipids and cholesteryl esters. Journal of Lipid Research 23 10721075CrossRefGoogle ScholarPubMed
Conte, G, Mele, M, Chessa, S, Castiglioni, B, Serra, A, Pagnacco, G & Secchiari, P 2010 Diacylglycerol acyltransferase 1, stearoyl-CoA desaturase 1, and sterol regulatory element binding protein 1 gene polymorphisms and milk fatty acid composition in Italian Brown cattle. Journal of Dairy Science 93 753763CrossRefGoogle ScholarPubMed
Couronne, O, Poliakov, A, Bray, N, Ishkhanov, T, Ryaboy, D, Rubin, E & Pachter, L 2003 Strategies and tools for whole-genome alignments. Genome Research 13 7380CrossRefGoogle ScholarPubMed
Fornage, M, Papanicolaou, G, Lewis, CE, Boerwinkle, E & Siscovick, DS 2010 Common INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle age. Metabolism 59 10841091CrossRefGoogle ScholarPubMed
Hara, A & Radin, NS 1978 Lipid extraction of tissues with a low-toxicity solvent. Analytical Biochemistry 90 420426CrossRefGoogle ScholarPubMed
Harvatine, KJ & Bauman, DE 2006 SREBP1 and thyroid hormone responsive spot 14 (S14) are involved in the regulation of bovine mammary lipid synthesis during diet-induced milk fat depression and treatment with CLA. Journal of Nutrition 136 24682474CrossRefGoogle ScholarPubMed
Harvatine, KJ, Boisclair, YR & Bauman, DE 2009 Recent advances in the regulation of milk fat synthesis. Animal 3 4054CrossRefGoogle ScholarPubMed
Jensen, RG 2002 The composition of bovine milk lipids: January 1995 to December 2000. Journal of Dairy Science 85 295350CrossRefGoogle ScholarPubMed
Keating, AF, Stanton, C, Murphy, JJ, Smith, TJ, Ross, RP & Cairns, MT 2005 Isolation and characterization of the bovine Stearoyl-CoAdesaturase promoter and analysis of polymorphisms in the promoter region in dairy cows. Mammary Genome 16 184193CrossRefGoogle ScholarPubMed
Kelsey, JA, Corl, BA, Collier, RJ & Bauman, DE 2003 The effect of breed, parity, and stage of lactation on conjugated linoleic acid (CLA) in milk fat from dairy cows. Journal of Dairy Science 86 25882597CrossRefGoogle ScholarPubMed
Kgwatalala, PM, Ibeagha-Awemu, EM, Mustafa, AF & Zhao, X 2009 Stearoyl-CoA desaturase 1 genotype and stage of lactation influences milk fatty acid composition of Canadian Holstein cows. Animal Genetics 40 609615CrossRefGoogle ScholarPubMed
Lengi, AJ & Corl, BA 2007 Identification and characterization of a novel bovine stearoyl-CoA desaturase isoform with homology to human SCD5. Lipids 42 499508CrossRefGoogle ScholarPubMed
Lock, AL & Garnsworthy, PC 2003 Seasonal variation in milk conjugated linoleic acid and Delta 9-desaturase activity in dairy cows. Livestock Production Science 79 4759CrossRefGoogle Scholar
McPherson, R & Gauthier, A 2004 Molecular regulation of SREBP function: the Insig-SCAP connection and isoform-specific modulation of lipid synthesis. Biochemistry and Cell Biology 82 201211CrossRefGoogle ScholarPubMed
Mele, M, Conte, G, Castiglioni, B, Chessa, S, Macciotta, NP, Serra, A, Buccioni, A, Pagnacco, G & Secchiari, P 2007 Stearoyl-coenzyme A desaturase gene polymorphism and milk fatty acid composition in Italian Holsteins. Journal of Dairy Science 90 44584465CrossRefGoogle ScholarPubMed
Mosley, EE & McGuire, MA 2007 Methodology for the in vivo measurement of the delta9-desaturation of myristic, palmitic, and stearic acids in lactating dairy cattle. Lipids 42 939945CrossRefGoogle ScholarPubMed
NRC (2001) National Research Council: Nutrient Requirements of Dairy Cattle. Washington DC, USAGoogle Scholar
O'Donnell-Megaro, AM, Barbano, DM & Bauman, DE 2011 Survey of the fatty acid composition of retail milk in the United States including regional and seasonal variations. Journal of Dairy Science 94 5965CrossRefGoogle ScholarPubMed
Ogorevc, J, Kunej, T, Razpet, A & Dovc, P 2009 Database of cattle candidate genes and genetic markers for milk production and mastitis. Animal Genetics 40 832851CrossRefGoogle ScholarPubMed
Palmquist, DL, Beaulieu, AD & Barbano, DM 1993 Feed and animal factors influencing milk fat composition. Journal of Dairy Science 76 17531771CrossRefGoogle ScholarPubMed
Palmquist, DL, Lock, AL, Shingfield, KJ & Bauman, DE 2005 Biosynthesis of conjugated linoleic acid in ruminants and humans. Advances in Food and Nutrition Research 50 179217CrossRefGoogle ScholarPubMed
Rincon, G, Farber, EA, Farber, CR, Nkrumah, JD & Medrano, JF 2009a Polymorphisms in the STAT6 gene and their association with carcass traits in feedlot cattle. Animal Genetics 40 878882CrossRefGoogle ScholarPubMed
Rincon, G, Islas-Trejo, A, Casellas, J, Ronin, Y, Soller, M, Lipkin, E & Medrano, JF 2009b Fine mapping and association analysis of a quantitative trait locus for milk production traits on Bos taurus autosome 4. Journal of Dairy Science 92 758774CrossRefGoogle ScholarPubMed
Rincon, G, Thomas, M & Medrano, JF 2007 SNP Identification of genes involved in GH-IGF1 signalling on BTA5. In: Plant & Animal Genomes XV Conference. San Diego CA, USAGoogle Scholar
Saltert, AM & Tarling, EJ 2007 Regulation of gene transcription by fatty acids. Animal 1 13141320CrossRefGoogle Scholar
Schennink, A, Stoop, WM, Visker, MH, Heck, JM, Bovenhuis, H, van der Poel, JJ, van Valenberg, HJ & van Arendonk, JA 2007 DGAT1 underlies large genetic variation in milk-fat composition of dairy cows. Animal Genetics 38 467473CrossRefGoogle ScholarPubMed
Shimano, H 2009 SREBPs: physiology and pathophysiology of the SREBP family. FEBS Journal 276 616621CrossRefGoogle ScholarPubMed
Soyeurt, H, Dardenne, P, Gillon, A, Croquet, C, Vanderick, S, Mayeres, P, Bertozzi, C & Gengler, N 2006 Variation in fatty acid contents of milk and milk fat within and across breeds. Journal of Dairy Science 89 48584865CrossRefGoogle ScholarPubMed
Soyeurt, H, Dehareng, F, Mayeres, P, Bertozzi, C & Gengler, N 2008 Variation of delta 9-desaturase activity in dairy cattle. Journal of Dairy Science 91 32113224CrossRefGoogle ScholarPubMed
Soyeurt, H, Gillon, A, Vanderick, S, Mayeres, P, Bertozzi, C & Gengler, N 2007 Estimation of heritability and genetic correlations for the major fatty acids in bovine milk. Journal of Dairy Science 90 44354442CrossRefGoogle ScholarPubMed
Stoop, WM, Schennink, A, Visker, MH, Mullaart, E, van Arendonk, JA & Bovenhuis, H 2009 Genome-wide scan for bovine milk-fat composition. I. Quantitative trait loci for short- and medium-chain fatty acids. Journal of Dairy Science 92 46644675CrossRefGoogle ScholarPubMed
Storey, J 2002 A direct approach to false discovery rates. Journal of the Royal Statistical Society B 64 479498CrossRefGoogle Scholar
Winter, A, Kramer, W, Werner, FA, Kollers, S, Kata, S, Durstewitz, G, Buitkamp, J, Womack, JE, Thaller, G & Fries, R 2002 Association of a lysine-232/alanine polymorphism in a bovine gene encoding acyl-CoA:diacylglycerol acyltransferase (DGAT1) with variation at a quantitative trait locus for milk fat content. Proceedings of the National Academy of Sciences USA 99 93009305CrossRefGoogle Scholar
Zavattari, P, Loche, A, Civolani, P, Pilia, S, Moi, L, Casini, MR, Minerba, L & Loche, S 2010 An INSIG2 polymorphism affects glucose homeostasis in Sardinian obese children and adolescents. Annals of Human Genetics 74 381386CrossRefGoogle ScholarPubMed