Skip to main content
SpringerLink
Log in

Polymorphism of CSN2 and TNF-α Genes in the Population of Holstein Cattle Bred in Ukraine

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

Abstract

Peculiarities of the genetic structure of the population of Holstein cattle bred in Ukraine were studied by beta-casein and tumor necrosis factor alpha loci. Using the methods of allele-specific PCR (AS-PCR) and PCR with restriction fragment length polymorphism (PCR-RFLP) analysis, polymorphism of the beta-casein gene (CSN2) by allelic variants A1 and A2 and of the tumor necrosis factor-alpha (TNF-α) by SacI-polymorphism in the promoter region of the gene (–824 A>G marker mutation) and RsaI-polymorphism in the fourth exon were analyzed. It was proven that both loci are polymorphic in the studied cattle population. For each of the polymorphic loci, the main genetic and population parameters of the Holstein cow population were established. For the CSN2 locus, a significant predominance of the frequency of the A2 allele over A1 was established (0.78 vs. 0.22). For the SacI- and RsaI-polymorphisms of TNF-α, maximal (1.980 and 1.988) values of the locus polymorphism level (the number of effective alleles) were detected. For both mutations in the TNF-α gene, actual parity in the frequency values of the corresponding alleles was established (0.55 and 0.45 for the SacI-polymorphism; 0.54 and 0.46 for the RsaI-polymorphism). For the RsaI-polymorphism in the TNF-α fourth exon, a deviation from the state of genetic equilibrium according to Hardy–Weinberg was recorded in the studied population of animals, and a significant excess of heterozygous individuals was detected (25%). Based on the results of the analysis of milk productivity parameters of individuals with different CSN2 locus genotypes, it was established that individuals with the A2A2 genotype are characterized by higher values of standard milk production as compared with individuals with the A1A1 genotype (p = 0.042). For the SacI- and RsaI-polymorphism of the TNF-α gene, there were no significant differences in the parameters of standard milk productivity for two lactations between individuals with different genotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

REFERENCES

  1. Antonopoulos, D., Vougiouklaki, D., Laliotis, G.P., Tsironi, T., Valasi, I., Chatzilazarou, A., Halvatsiotis, P., and Houhoula, D., Identification of polymorphisms of the CSN2 gene encoding β-casein in greek local breeds of cattle, Vet. Sci., 2021, vol. 8, p. 257. https://doi.org/10.3390/vetsci8110257

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bojarojć-Nosowicz, B., Kaczmarczyk, E., Stachura, A., and Kotkiewicz, M., Polymorphism in the promoter region of the tumor necrosis factor-alpha gene in cattle herds naturally infected and uninfected with the Bovine Leukemia Virus, Pol. J. Vet. Sci., 2011, vol. 14, no. 4, pp. 671—673. https://doi.org/10.2478/v10181-011-0101-0

    Article  CAS  PubMed  Google Scholar 

  3. Bojarojć-Nosowicz, B., Kaczmarczyk, E., and Jastrzebska, A., Relationship between polymorphism in the tumour necrosis factor-alpha gene and selected indices and cell subpopulations in naturally bovine leukaemia virus-infected and healthy cows, Vet. Med., 2018, vol. 63, no. 3, pp. 101—109. https://doi.org/10.17221/135/2017-VETMED

    Article  Google Scholar 

  4. Brajnik, Z. and Ogorevc, J., Candidate genes for mastitis resistance in dairy cattle: a data integration approach, J. Anim. Sci. Biotechnol., 2023, vol. 14, p. 10. https://doi.org/10.1186/s40104-022-00821-0

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cheng, Y., Huang, C.S., and Tsai, H.-J., Relationship of bovine TNF-α gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle, J. Vet. Med. Sci., 2016, vol. 78, no. 5, pp. 727–732. https://doi.org/10.1292/jvms.15-0506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cieślińska, A., Fiedorowicz, E., Zwierzchowski, G., Kordulewska, N., Jarmołowska, B., and Kostyra, E., Genetic polymorphism of β-casein gene in polish red cattle—preliminary study of A1 and A2 frequency in genetic conservation herd, Animals (Basel), 2019, vol. 9, no. 6, p. 377. https://doi.org/10.3390/ani9060377

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cieślińska, A., Fiedorowicz, E., Rozmus, D., Sienkiewicz-Szłapka, E., Jarmołowska, B., and Kamiński, S., Does a little difference make a big difference? Bovine β-casein A1 and A2 variants and human health—an update, Int. J. Mol. Sci., 2022, vol. 23, p. 15637. https://doi.org/10.3390/ijms232415637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dai, R., Fang, Y., Zhao, W., Liu, S., Ding, J., Xu, K., Yang, L., He, C., Ding, F., and Meng, H., Identification of alleles and genotypes of beta casein with DNA sequencing analysis in Chinese Holstein cow, J. Dairy Res., 2016, vol. 83, no. 3, pp. 312–316. https://doi.org/10.1017/S0022029916000303

    Article  CAS  PubMed  Google Scholar 

  9. Fernández-Rico, S., Mondragón, A.D.C., López-Santamarina, A., Cardelle-Cobas, A., Regal, P., Lamas, A., Ibarra, I.S., Cepeda, A., and Miranda, J.M., A2 milk: new perspectives for food technology and human health, Foods., 2022, vol. 11, no. 16, p. 2387. https://doi.org/10.3390/foods11162387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gogoi, A., Das, B., Chabukdhara, P., Phookan, A., and Phangchopi, D., Livestock breeding for disease resistance: a perspective review, Agric. Rev., 2021, vol. 43, pp. 116–121. https://doi.org/10.18805/ag.R-2169

    Article  Google Scholar 

  11. Grażyna, S., Korwin-Kossakowska Pawlik, A., Hameed, A., Abdel, K.G., and Jolanta, O., Genetic basis of mastitis resistance in dairy cattle—A review, Ann. Anim. Sci., 2013, vol. 13, no. 4, pp. 663–673. https://doi.org/10.2478/aoas-2013-0043

    Article  Google Scholar 

  12. Hanusová, E., Huba, J., Oravcová, M., Polák, P., and Vrtková, I., Genetic variants of beta-casein in Holstein dairy cattle in Slovakia, Slovak J. Anim. Sci., 2010, vol. 43, no. 2, pp. 63–66.

    Google Scholar 

  13. Higuchi, M., Miyashita, N., and Awata, T., Rapid communication: a PCR-RFLP in the coding region of the bovine tumor necrosis factor-µ locus, J. Anim. Sci., 1999, vol. 77, no. 12, pp. 3400–3401. https://doi.org/10.2527/1999.77123400x

    Article  CAS  PubMed  Google Scholar 

  14. Ivanković, A., Pećina, M., Ramljak, J., and Pašić, V, Genetic polymorphism and effect on milk production of CSN2 gene in conventional and local cattle breeds in Croatia, Mljekarstvo, 2021, vol. 71, no. 1, pp. 3–12. https://doi.org/10.15567/mljekarstvo.2021.0101

    Article  Google Scholar 

  15. Jiménez-Montenegro, L., Alfonso, L., Mendizabal, J.A., and Urrutia, O., Worldwide research trends on milk containing only A2 β-casein: A bibliometric study, Animals, 2022, vol. 12, no. 15, p. 1909. https://doi.org/10.3390/ani12151909

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kamiński, S., Zabolewicz, T., Oleński, K., and Babuchowski, A., Long-term changes in the frequency of beta-casein, kappa-casein and beta-lactoglobulin alleles in Polish Holstein-Friesian dairy cattle, Anim. Feed Sci., 2023, vol. 32, no. 2, pp. 205–210. https://doi.org/10.22358/jafs/157531/2023

    Article  Google Scholar 

  17. Kaskous, S., A1- and A2-milk and their effect on human health, J. Food Eng. Technol., 2020, vol. 9, no. 1, pp. 15–21. https://doi.org/10.32732/jfet.2020.9.1.15

    Article  Google Scholar 

  18. Kay, S.I.S., Delgado, S., Mittal, J., Eshraghi, R.S., Mittal, R., and Eshraghi, A.A., Beneficial effects of milk having A2 β-casein protein: myth or reality?, J. Nutr., 2021, vol. 151, no. 5, pp. 1061–1072. https://doi.org/10.1093/jn/nxaa454

    Article  CAS  PubMed  Google Scholar 

  19. Konnai, S., Usui, T., Ikeda, M., Kohara, J., Hirata, T., Okada, K., Ohashi, K., and Onuma, M., Tumor necrosis factor-alpha genetic polymorphism may contribute to progression of bovine leukemia virus-infection, Microbes Infect., 2006, vol. 8, no. 8, pp. 2163–2171. https://doi.org/10.1016/j.micinf.2006.04.017

    Article  CAS  PubMed  Google Scholar 

  20. Kuellenberg de Gaudry, D., Lohner, S., Bischoff, K., Schmucker, C., Hoerrlein, S., Roeger, C., and Meerpohl, J.J., A1- and A2 beta-casein on health-related outcomes: a scoping review of animal studies, Eur. J. Nutr., 2021, vol. 61, no. 1, pp. 1–21. https://doi.org/10.1007/s00394-021-02551-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kulibaba, R., Sakhatskyi, M., and Liashenko, Yu., Comparative analysis of A1 and A2 allele detection efficiency for bovine CSN2 gene by AS-PCR methods, Acta Biochim. Pol., 2023, vol. 70, no. 1, pp. 205–209. https://doi.org/10.18388/abp.2020_6530

    Article  CAS  PubMed  Google Scholar 

  22. Kumar, A., Singh, R.V., Chauhan, A., Ilayakumar, K., Kumar, S., Kumar, A., and Bhushan, B., Genetic association analysis reveals significant effect of β-casein A1/A2 loci on production & reproduction traits in Frieswal crossbred cows, Biol. Rhythm Res., 2019, no. 8, pp. 1–14. https://doi.org/10.1080/09291016.2019.1571705

  23. Kumar, R., Kadirvel, G., Das, M., Puro, K., Katiyar, R., Singh, M., Lyngdoh, E., and Mishra, V.K., A1 and A2 Milk: Myth vs. Reality – A mini review, Indian J. Hill Farming., 2021, vol. 34, no. 2, pp. 249—254.

    Google Scholar 

  24. Ladyka, V., Pavlenko, Y., and Sklyarenko, Y., β-casein gene polymorphism use in terms of brown dairy cattle preservation, Arch. Zootec., 2021, vol. 70, no. 269, pp. 88–94. https://doi.org/10.21071/az.v70i269.5422

    Article  CAS  Google Scholar 

  25. Mencarini, I.R., Woodford, K.B., and Old, K.M., Comparing herd selection strategies for A2 beta-casein, Proc. N. Z. Soc. Anim. Prod., 2013, vol. 73, pp. 149–154.

    Google Scholar 

  26. Miluchová, M., Gábor, M., and Candrák, J., The effect of the genotypes of the CSN2 gene on test-day milk yields in the Slovak Holstein cow, Agriculture, 2023, vol. 13, no. 1, p. 154. https://doi.org/10.3390/agriculture13010154

    Article  CAS  Google Scholar 

  27. Mohsen, T.U. and Al-Khuzai, H.M.H., Effect of TNF-α gene polymorphism on fertility insufficiency in Holstein cows, Int. J. Health Sci., 2022, vol. 6, no. S4, pp. 8066–8070. https://doi.org/10.53730/ijhs.v6nS4.10411

    Article  Google Scholar 

  28. Mrode, R., Ojango, J.M.K., Okeyo, A.M., and Mwacharo, J.M., Genomic selection and use of molecular tools in breeding programs for indigenous and crossbred cattle in developing countries: current status and future prospects, Front. Genet., 2019. vol. 9, p. 694. https://doi.org/10.3389/fgene.2018.00694

    Article  PubMed  PubMed Central  Google Scholar 

  29. Olenski, K., Kamiński, S., Szyda, J., and Cieslinska, A., Polymorphism of the beta-casein gene and its associations with breeding value for production traits of Holstein-Friesian bulls, Livestock Sci., 2010, vol. 131, no. 1, pp. 137–140. https://doi.org/10.1016/j.livsci.2010.02.023

    Article  Google Scholar 

  30. Pal, A. and Chakravarty, A.K., Disease resistance for different livestock species, in Genetics and Breeding for Disease Resistance of Livestock, 2020, pp. 271–296. https://doi.org/10.1016/B978-0-12-816406-8.00019-X

  31. Peakall, R. and Smouse, P.E., GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research—an update, Bioinformatics, 2012, vol. 28, pp. 2537–2539. https://doi.org/10.1093/bioinformatics/bts460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ristanic, M., Glavinic, U., Vejnovic, B., et al., Beta-casein gene polymorphism in Serbian Holstein-Friesian cows and its relationship with milk production traits, Acta Vet., 2020, vol. 70, no. 4, pp. 497–510. https://doi.org/10.2478/acve-2020-0037

    Article  Google Scholar 

  33. Şahin, O., Boztepe, S., and Aytekin, I., A1 and A2 bovine milk, the risk of beta-casomorphin-7 and its possible effects on human health: (I) A1 and A2 milk and the risk of beta-casomorphin-7, Selcuk J. Agric. Food Sci., 2018, vol. 32, no. 3, pp. 632–639. https://doi.org/10.15316/SJAFS.2018.146

    Article  Google Scholar 

  34. Saranya, G.N., de Jong, E., Schenkel, F.S., Fonseca, P.A.S., Chud, T.C.S., Powell, D., Wachoski-Dark, G., Ronksley, P.E., Miglior, F., Orsel, K., and Barkema, H.W., Underlying genetic architecture of resistance to mastitis in dairy cattle: a systematic review and gene prioritization analysis of genome-wide association studies, J. Dairy Sci., 2023, vol. 106, no. 1, pp. 323–351. https://doi.org/10.3168/jds.2022-21923

    Article  CAS  Google Scholar 

  35. Sattar, H., Firyal, S., Awan, A.R., Rehman, H.U., Hasni, M.S., and Aqib, A.I., Genetic association of bovine TNF-α gene polymorphism with clinical and sub-clinical mastitis in Sahiwal cows, Pak. J. Zool., 2019, vol. 15, no. 6, pp. 1–4. https://doi.org/10.17582/journal.pjz/2019.51.6.sc2

    Article  CAS  Google Scholar 

  36. Sebastiani, C., Arcangeli, C., Ciullo, M., Torricelli, M., Cinti, G., Fisichella, S., and Biagetti, M., Frequencies evaluation of β-casein gene polymorphisms in dairy cows reared in Central Italy, Animals, 2020, vol. 10, no. 2, p. 252. https://doi.org/10.3390/ani10020252

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sebastiani, C., Arcangeli, C., Torricelli, M., Ciullo,M., D’avino, N., Cinti, G., Fisichella, S., and Biagetti, M., Marker-assisted selection of dairy cows for β-casein gene A2 variant, Ital. J. Food Sci., 2022, vol. 34, no. 2, pp. 21–27. https://doi.org/10.15586/ijfs.v34i2.2178

    Article  CAS  Google Scholar 

  38. Singh, U., Deb, R., Alyethodi, R.R., Alex, R., Kumar, S., Chakraborty, S., and Sharma, A., Molecular markers and their applications in cattle genetic research: a review, Biomarkers Genomic Med., 2014, vol. 6, no. 2, pp. 49–58. https://doi.org/10.1016/j.bgm.2014.03.001

    Article  CAS  Google Scholar 

  39. Soyudal, B., Ardicli, S., Samli, H., Dincel, D., and Balci, F., Association of polymorphisms in the CSN2,CSN3, LGB and LALBA genes with milk production traits in Holstein cows raised in Turkey, J. Hellenic Vet. Med. Soc., 2019, vol. 69, no. 4, pp. 1271–1282. https://doi.org/10.12681/jhvms.19617

    Article  Google Scholar 

  40. Suprovych, T.M., Salyha, Yu.T., Suprovych, M.P., Fedorovych, E.I., Fedorovych, V.V., and Chornyj, I.O., Genetic polymorphism of BoLA-DRB3.2 locus in Ukrainian cattle breeds, Cytol. Genet., 2022, vol. 56, no. 4, pp. 319–330. https://doi.org/10.3103/S0095452722040089

    Article  Google Scholar 

  41. Thirupathy, V.R., Pramod, S., Lasna, S., and Bibin, B., Impact of A1/A2 milk on health: facts and implications, Dairy Vet. Sci. J., 2019, vol. 9, no. 3, p. 555761. https://doi.org/10.19080/JDVS.2019.09.555761

    Article  Google Scholar 

  42. Thiruvengadam, M., Venkidasamy, B., Thirupathi, P., Chung, I.M., and Subramanian, U., β-Casomorphin: a complete health perspective, Food Chem., 2020, vol. 337, p. 127765. https://doi.org/10.1016/j.foodchem.2020.127765

    Article  CAS  PubMed  Google Scholar 

  43. Wakchaure, R., Ganguly, S., Praveen, P.K., Kumar, A., and Sharma, S., Marker assisted selection (MAS) in animal breeding: a review, J. Drug Metab. Toxicol., 2015, vol. 6, p. e127. https://doi.org/10.4172/2157-7609.1000e127

    Article  CAS  Google Scholar 

  44. Weigel, K.A. and Shook, G.E., Genetic selection for mastitis resistance, Vet. Clin. North Am.: Food Anim. Pract., 2018, vol. 34, no. 3, pp. 457–472. https://doi.org/10.1016/j.cvfa.2018.07.001

    Article  PubMed  Google Scholar 

  45. Wojdak-Maksymiec, K., Szyda, J.,and Strabel,T., Paritydependent association between TNF-α and LTF gene polymorphisms and clinical mastitis in dairy cattle, BMC Vet. Res., 2013, vol. 9, p. 114. https://doi.org/10.1186/1746-6148-9-114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yudin, N.S., Aitnazarov, R.B., Voevoda, M.I., Gerlinskaya, L.A., and Moshkin, M.P., Association of polymorphism harbored by tumor necrosis factor alpha gene and sex of calf with lactation performance in cattle, Asian-Australas. J. Anim. Sci., 2013, vol. 26, no. 10, pp. 1379–1387. https://doi.org/10.5713/ajas.2013.13114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zalewska, M., Puppel, K., and Sakowski, T., Associations between gene polymorphisms and selected meat traits in cattle—a review, Anim. Biosci., 2021, vol. 34, no. 9, pp. 1425–1438. https://doi.org/10.5713/ab.20.0672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The studies were carried out within the research work on the topic no. 110/8-pr-2022 “Development of the Technology of Molecular Genetic Support of the Selection Process for Creating the Herds of Cows Producing the A2 Milk.”

Author information

Authors and Affiliations

  1. National University of Life and Environmental Sciences of Ukraine, 03041, Kyiv, Ukraine

    R. O. Kulibaba & M. I. Sakhatskyi

  2. Institute of Animal Science, National Academy of Agrarian Sciences of Ukraine, 61026, Kharkiv, Ukraine

    Yu. V. Liashenko

Authors
  1. R. O. Kulibaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu. V. Liashenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. I. Sakhatskyi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. O. Kulibaba.

Ethics declarations

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The studies were carried out using whole blood as a source of biological material, which was obtained from the veterinary service of the farm for breeding and keeping cattle. Therefore, they did not need ethical approval.

Additional information

Publisher’s Note.

Allerton Press remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kulibaba, R.O., Liashenko, Y.V. & Sakhatskyi, M.I. Polymorphism of CSN2 and TNF-α Genes in the Population of Holstein Cattle Bred in Ukraine. Cytol. Genet. 58, 29–38 (2024). https://doi.org/10.3103/S0095452724010055

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0095452724010055

Search

Navigation