Abstract
The aim of this study was to identify candidate genes associated with milk fat per cent and fatty acid (FA) composition in Vrindavani cattle using the Illumina 50 K single-nucleotide polymorphism (SNP) array. After quality control, a total of 41,427 informative and high-quality SNPs were used for a genome-wide association study (GWAS) for milk fat percentage and 16 different types of fatty acids. Lactation stage, parity, test day milk yield, and proportion of exotic inheritance were included as fixed effects in the GWAS model. A total of 67 genome-wide significant (P < 1.20 × 10−06) SNPs and 176 suggestive significant (P < 2.41 × 10−05) SNPs were identified. Out of these, 15 SNPs were associated with more than one trait. The strongest associations were found on BTA14 for milk fat percentage and on BTA2 and BTA16 for polyunsaturated fatty acids. Several significant SNPs were identified close to or within the genes ELOVL6, FABP4, PMP2, PLIN1, MFGE8, GHRL2, and LDLRAD3 which are known to be associated with fat percentage and FA composition in dairy cattle breeds. This study is a step forward to better characterize the molecular mechanisms of phenotypic variation in milk fatty acids in a taurine–indicine composite cattle breed reared in tropical environments.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The 50 K SNP chip data of the Vrindavani cattle used in this study have been uploaded to Figshare (DOI, https://doi.org/10.6084/m9.figshare.12808343.v2).
References
Alexander, D.H., Novembre, J. and Lange, K., 2009. Fast model-based estimation of ancestry in unrelated individuals. Genome research, 19, 1655-1664.doi: https://doi.org/10.1101/gr.094052.109.
Aoki, N., Ishii, T., Ohira, S., Yamaguchi, Y., Negi, M., Adachi, T., Nakamura, R. and Matsuda, T., 1997. Stage specific expression of milk fat globule membrane glycoproteins in mouse mammary gland: comparison of MFG-E8, butyrophilin, and CD36 with a major milk protein, β-casein. Biochimica et Biophysica Acta (BBA)-General Subjects, 1334, 182-190. doi: https://doi.org/10.1016/s0304-4165(96)00091-8.
Bionaz, M. and Loor, J.J., 2008. ACSL1, AGPAT6, FABP3, LPIN1, and SLC27A6 are the most abundant isoforms in bovine mammary tissue and their expression is affected by stage of lactation. The Journal of nutrition, 138, 1019-1024. https://doi.org/10.1093/jn/138.6.1019.
Buitenhuis, B., Janss, L.L., Poulsen, N.A., Larsen, L.B., Larsen, M.K. and Sørensen, P., 2014. Genome wide association and biological pathway analysis for milk-fat composition in Danish Holstein and Danish Jersey cattle. BMC genomics, 15, 1-11. https://doi.org/10.3168/jds.2017-13225.
Caroli, A.M., Chessa, S. and Erhardt, G.J., 2009. Invited review: Milk protein polymorphisms in cattle: Effect on animal breeding and human nutrition. Journal of dairy science, 92, 5335-5352.
Cole, J.B., Wiggans, G.R., Ma, L., Sonstegard, T.S., Lawlor, T.J., Crooker, B.A., Van Tassell, C.P., Yang, J., Wang, S., Matukumalli, L.K. and Da, Y., 2011. Genome-wide association analysis of thirty one production, health, reproduction and body conformation traits in contemporary US Holstein cows. BMC genomics, 12, 408. https://doi.org/10.1186/1471-2164-12-408.
Coppa, M., Ferlay, A., Monsallier, F., Verdier-Metz, I., Pradel, P., Didienne, R., Farruggia, A., Montel, M.C. and Martin, B., 2011. Milk fatty acid composition and cheese texture and appearance from cows fed hay or different grazing systems on upland pastures. Journal of dairy science, 94, 1132-1145. https://doi.org/10.3168/jds.2010-3510.
Gebreyesus, G., Buitenhuis, A.J., Poulsen, N.A., Visker, M.H.P.W., Zhang, Q., Van Valenberg, H.J.F., Sun, D. and Bovenhuis, H., 2019. Multi-population GWAS and enrichment analyses reveal novel genomic regions and promising candidate genes underlying bovine milk fatty acid composition. Bmc Genomics, 20, 178. https://doi.org/10.1186/s12864-019-5573-9.
Gondro C., 2015. Primer to analysis of genomic data using R. New York, NY: Springer.
Han, B., Kang, H.M. and Eskin, E., 2009. Rapid and accurate multiple testing correction and power estimation for millions of correlated markers. PLoS Genet, 5, 1000456. https://doi.org/10.1371/journal.pgen.1000456.
Haug, A., Høstmark, A.T. and Harstad, O.M., 2007. Bovine milk in human nutrition–a review. Lipids in health and disease, 6, 25. https://doi.org/10.1186/1476-511X-6-25.
Ibeagha-Awemu, E.M., Peters, S.O., Akwanji, K.A., Imumorin, I.G. and Zhao, X., 2016. High density genome wide genotyping-by-sequencing and association identifies common and low frequency SNPs, and novel candidate genes influencing cow milk traits. Scientific reports, 6, 31109. https://doi.org/10.1038/srep31109.
Jakobsson, A., Westerberg, R. and Jacobsson, A., 2006. Fatty acid elongases in mammals: their regulation and roles in metabolism. Progress in lipid research, 45, 237-249. https://doi.org/10.1016/j.plipres.2006.01.004.
Jiang, J., Ma, L., Prakapenka, D., VanRaden, P.M., Cole, J.B. and Da, Y., 2019. A large-scale genome-wide association study in US Holstein cattle. Frontiers in genetics, 10, 412. https://doi.org/10.3389/fgene.2019.00412.
Junjvlieke, Z., Mei, C.G., Khan, R., Zhang, W.Z., Hong, J.Y., Wang, L., Li, S.J. and Zan, L.S., 2019. Transcriptional regulation of bovine elongation of very long chain fatty acids protein 6 in lipid metabolism and adipocyte proliferation. Journal of cellular biochemistry, 120, 13932-13943. https://doi.org/10.1002/jcb.28667.
Knutsen, T.M., Olsen, H.G., Tafintseva, V., Svendsen, M., Kohler, A., Kent, M.P. and Lien, S., 2018. Unravelling genetic variation underlying de novo-synthesis of bovine milk fatty acids. Scientific reports, 8, 1-13. https://doi.org/10.1038/s41598-018-20476-0.
Lander, E. and Kruglyak, L., 1995. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature genetics, 11, 241-247. https://doi.org/10.1038/ng1195-241.
Li, C., Sun, D., Zhang, S., Wang, S., Wu, X., Zhang, Q., Liu, L., Li, Y. and Qiao, L., 2014. Genome wide association study identifies 20 novel promising genes associated with milk fatty acid traits in Chinese Holstein. PloS one, 9, 96186. https://doi.org/10.1371/journal.pone.0096186.
Matsuzaka, T. and Shimano, H., 2009. Elovl6: a new player in fatty acid metabolism and insulin sensitivity. Journal of molecular medicine, 87, 379-384. https://doi.org/10.1007/S00109-009-0449-0.
Mensink, R.P., Zock, P.L., Kester, A.D. and Katan, M.B., 2003. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. The American journal of clinical nutrition, 77, 1146-1155. https://doi.org/10.1093/ajcn/77.5.1146.
Minozzi, G., Williams, J.L., Stella, A., Strozzi, F., Luini, M., Settles, M.L., Taylor, J.F., Whitlock, R.H., Zanella, R. and Neibergs, H.L., 2012. Meta-analysis of two genome-wide association studies of bovine paratuberculosis. PLoS one, 7, 32578.
Nafikov, R.A., Schoonmaker, J.P., Korn, K.T., Noack, K., Garrick, D.J., Koehler, K.J., Minick-Bormann, J., Reecy, J.M., Spurlock, D.E. and Beitz, D.C., 2013. Association of polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) and fatty acid-binding protein-3 and fatty acid-binding protein-4 (FABP3 and FABP4) with fatty acid composition of bovine milk. Journal of dairy science, 96, 6007-6021. https://doi.org/10.3168/jds.2013-6703.
O’Fallon, J.V., Busboom, J.R., Nelson, M.L. and Gaskins, C.T., 2007. A direct method for fatty acid methyl ester synthesis: application to wet meat tissues, oils, and feedstuffs. Journal of animal science, 85, 1511-1521.doi: https://doi.org/10.2527/jas.2006-491.
Palombo, V., Milanesi, M., Sgorlon, S., Capomaccio, S., Mele, M., Nicolazzi, E., Ajmone-Marsan, P., Pilla, F., Stefanon, B. and D'Andrea, M., 2018. Genome-wide association study of milk fatty acid composition in Italian Simmental and Italian Holstein cows using single nucleotide polymorphism arrays. Journal of dairy science, 101, 11004-11019. doi: https://doi.org/10.3168/jds.2018-14413.
Pegolo, S., Cecchinato, A., Mele, M., Conte, G., Schiavon, S. and Bittante, G., 2016. Effects of candidate gene polymorphisms on the detailed fatty acids profile determined by gas chromatography in bovine milk. Journal of Dairy Science, 99, 4558-4573. https://doi.org/10.3168/jds.2015-104209.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., De Bakker, P.I., Daly, M.J. and Sham, P.C., 2007. PLINK: a tool set for whole-genome association and population-based linkage analyses. The American journal of human genetics, 81, 559-575. doi: https://doi.org/10.1086/519795.
Rønholt, S., Mortensen, K. and Knudsen, J.C., 2013. The effective factors on the structure of butter and other milk fat‐based products. Comprehensive Reviews in Food Science and Food Safety, 12, 468-482. https://doi.org/10.1111/1541-4337.12022.
Silva-Vignato, B., Coutinho, L.L., Cesar, A.S., Poleti, M.D., Regitano, L.C. and Balieiro, J.C., 2017. Comparative muscle transcriptome associated with carcass traits of Nellore cattle. BMC genomics, 18, 506. https://doi.org/10.1186/S12864-017-3897-X.
Singh, A., Mehrotra, A., Gondro, C., da Silva Romero, A.R., Pandey, A.K., Karthikeyan, A., Bashir, A., Mishra, B.P., Dutt, T. and Kumar, A., 2020. Signatures of Selection in Composite Vrindavani Cattle of India. Frontiers in genetics, 11. doi: https://doi.org/10.3389/fgene.2020.589496
Wang, W., Wu, X. and Tian, Y., 2015. Crosstalk of AP4 and TGFβ receptor signaling in NSCLC. Tumor Biology, 36, 447-452. doi: https://doi.org/10.1007/s13277-014-2674-6.
Watanabe, S., Iimori, M., Chan, D.V., Hara, E., Kitao, H. and Maehara, Y., 2018. MDC1 methylation mediated by lysine methyltransferases EHMT1 and EHMT2 regulates active ATM accumulation flanking DNA damage sites. Scientific reports, 8, 1-10. https://doi.org/10.1038/s41598-018-31427-0.
Acknowledgements
The authors thank the director of IVRI and the staff at the Cattle and Buffalo farm at IVRI. This project was supported by the CAAST-ACLH project of NAHEP.
Author information
Authors and Affiliations
Contributions
Conceived and designed the experiments: AK. Performed the experiments: AS, KA, and AKP. Analysed the data: AS, AK, CG, ARSR, and AM. Contributed reagents/materials/analysis tools: TD. Wrote the paper: AS and AK. Edited the paper: CG, AK, and BPM.
Corresponding author
Ethics declarations
Ethics approval
This study was conducted following the regulations set out by the Institutional Animal Ethics Committee (IAEC) of the Indian Veterinary Research Institute, Bareilly.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Singh, A., Kumar, A., Gondro, C. et al. Identification of genes affecting milk fat and fatty acid composition in Vrindavani crossbred cattle using 50 K SNP-Chip. Trop Anim Health Prod 53, 347 (2021). https://doi.org/10.1007/s11250-021-02795-z
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11250-021-02795-z