Association of BoLA-DRB3.2 alleles with fusobacteriosis in cows

Keywords: necrobacteriosis, Major Histocompatibility Complex; alleles; PCR-RLFP; lameness; cattle.


The Major Histocompatability Complex (MHC) determines the immune response to pathogens, and its genes are promising candidates for the search of associations with diseases. A special role is played by BoLA-DRB3 gene, the product of which directly participates in the binding of alien antigens and conditions the specificity of the immune response. The second exon of this gene codes β1-domain of class II antigens, which is necessary for binding a broad spectrum of alien antigens. Exon 2 of BoLA-DRB3 gene is extremely polymorphic, giving the possibility to search the associations of its alleles with various diseases. The article provides the results of the study on polymorphism of alleles of BoLA-DRB3.2 gene for detection of its associations with sensitivity to fusobacteriosis (necrobacteriosis) of cows. The survey was performed using PCR-RFLP method with DNA of blood from 176 cows of two herds of Ukrainian black-and-white dairy breed. As a result of the studies, in the first herd, 25 BoLA-DRB3.2 alleles were found. In the selections of nectobacteriosis susceptible and resistant cows, we found 22 and 21 variants respectively. In the second herd, in the general selection and group of healthy animals, 27 alleles were typed, and 22 in the group of susceptible cows. BoLA-DRB3.2*22 allele was the commonest in both herds in both general selections and groups of nectobacteriosis-resistant cows. In the selection of susceptible animals, the commonest was the variant BoLA-DRB3.2*16. We determined statistically significant associations of BoLA-DRB3.2 alleles with sensitivity to nectobacteriosis of cattle. BoLA-DRB3.2*03 and *22 alleles associate with nectobacteriosis-resistant, while *16 and *23 – with nectobacteriosis-susceptible cows of the both studied groups. Also, in the first herd, another allele was found – *24, indicating close relationship with the disease. The studies of polymorphism of BoLA-DRB3 gene expand the knowledge about genetic peculiarities of the Ukrainian black-and-white dairy breed. The identified molecular-genetic markers could be useful for breeders whose work is oriented towards the formation of herds which are resistant to diseases of the limbs in cattle.


Behl, J. D., Verma, N. K., Tyagi, N., Mishra, P., Behl, R., & Joshi, B. K. (2012). The major histocompatibility complex in bovines: A review. ISRN Veterinary Science, 2012, 872710.

Boettcher, P. J., Dekkers, J. C., & Warnick, L. D., Wells, S. J. (1998). Genetic analysis of clinical lameness in dairy cattle. Journal of Dairy Science, 81(4), 1148–1156.

Buitenhuis, A. J., Lund, M. S., Thomasen, J. R., Thomsen, B., Nielsen, V. H., Bendixen, C., & Guldbrandtsen, B. (2007). Detection of quantitative trait loci affecting lameness and leg conformation traits in Danish Holstein cattle. Journal of Dairy Science, 90(1), 472–481.

Cha, E., Hertl, J. A., Bar, D., & Gröhn, Y. T. (2010). The cost of different types of lameness in dairy cows calculated by dynamic programming. Preventive Veterinary Medicine, 97, 1–8.

Dietz, A. B., Cohen, N. D., Timms, L., & Kehrli, M. E. (1997). Bovine lymphocyte antigen class II alleles as risk factors for high somatic cell counts in milk of lactating dairy cows. Journal of Dairy Science, 80(2), 406–412.

Duangjinda, M., Jindatajak, Y., Tipvong, W., Sriwarothai, J., Pattarajinda, V., Katawatin, S., & Boonkum, W. (2013). Association of BoLA-DRB3 alleles with tick-borne disease tolerance in dairy cattle in a tropical environment. Veterinary Parasitology, 196(3–4), 314–320.

Escayg, A. P., Hickford, J. G., & Bullock, D. W. (1997). Association between alleles of the ovine major histocompatibility complex and resistance to footrot. Research in Veterinary Science, 63(3), 283–287.

Ettema, J. F., & Østergaard, S. (2006). Economic decision making on prevention and control of clinical lameness in Danish dairy herds. Livestock Science, 102, 92–106.

Ferchichi, M. A., Jemmali, B., Amiri, S., Bejaoui, S., Ben Gara, A., & Rekik, B. (2018a). Association of lameness incidence and FGf-2 polymorphism. Journal of New Sciences, Sustainable Livestock Management, 9(4), 196–201.

Ferchichi, M. A., Jemmali, B., Amiri, S., Ben Gara, A., & Rekik, B. (2018b). Effect of leptin genetic polymorphism on lameness prevalence in Tunisian Holstein cows. Archives Animal Breeding, 61, 305–310.

Gelhaus, A., Schnittger, L., Mehlitz, D., Horstmann, R. D., & Meyer, C. G. (1995). Sequence and PCR-RFLP analysis of 14 novel BoLA-DRB3 alleles. Animal Genetics, 26(3), 147–153.

Gutiérrez, S. E., Esteban, E. N., Lützelschwab, C. M., & Juliarena, M. A. (2017). Major histocompatibility complex-associated resistance to infectious diseases: The case of bovine leukemia virus infection. Trends and Advances in Veterinary Genetics, 2017, 65804.

Hedges, J., Blowey, R. W., Packington, A. J., O’Callaghan, C. J., & Green, L. E. (2001). A longitudinal field trial of the effect of biotin on lameness in dairy cows. Journal of Dairy Science, 84(9), 1969–1975.

Heringstad, B., Egger-Danner, C., Charfeddine, N., Pryce, J. E., Stock, K. F., Kofler, J., Sogstad, A. M., Holzhauer, M., Fiedler, A., Müller, K., Nielsen, P., Thomas, G., Gengler, N., de Jong, G., Ødegård, C., Malchiodi, F., Miglior, F., Alsaaod, M., & Cole J. B. (2018). Invited review: Genetics and claw health: Opportunities to enhance claw health by genetic selection. Journal of Dairy Science, 101, 1–21.

Ibeagha-Awemu, E. M., Kgwatalala, P., Ibeagha, A. E., & Zhao, X. (2008). A critical analysis of disease-associated DNA polymorphisms in the genes of cattle, goat, sheep, and pig. Mammalian Genome, 19(4), 226–245.

Kulberg, S., Heringstad, B., Guttersrud, O. A., & Olsaker, I. (2007). Study on the association of BoLA-DRB3.2 alleles with clinical mastitis in Norwegian Red cows. Journal of Animal Breeding and Genetics, 124(4), 201–217.

Kumari, N., Loat, S., Saini, S., Dhilor, N., Kumar, A., & Kataria, R. S. (2019). Role of BoLA-DRB3 genetic diversity against resistance to mastitis in cattle: Review. Journal of Veterinary Science and Research, 1, 30–36.

Lei, W., Liang, Q., Jing, L., Wang, C., Wu, X., & He, H. (2012). BoLA-DRB3 gene polymorphism and FMD resistance or susceptibility in Wanbei cattle. Molecular Biology Reports, 39(9), 9203–9209.

Maillard, J. C., Renard, C., Chardon, P., Chantal, I., & Bensaid, A. (1999). Characterization of 18 new BoLA-DRB3 alleles. Animal Genetics, 30, 200–203.

Nascimento, C. S., Machado, M. A., Martinez, M. L., Silva, M., Guimarães, M., Campos, A., Azevedo, A., Teodoro, R., Verneque, R., Guimarães, S., & Oliveira, D. (2006). Association of the bovine major histocompatibility complex (BoLA) BoLA-DRB3 gene with fat and protein production and somatic cell score in Brazilian Gyr dairy cattle (Bos indicus). Genetics and Molecular Biology, 29(4), 641–647.

Oikonomou, G., Michailidis, G., Kougioumtzis, A., Avdi, M., & Banos, G. (2011). Effect of polymorphisms at the STAT5A and FGF2 gene loci on reproduction, milk yield and lameness of Holstein cows. Research in Veterinary Science, 91(2), 235–239.

Ózsvári, L. (2017). Economic cost of lameness in dairy cattle herds. Journal of Dairy, Veterinary and Animal Research, 6(2), 00176.

Peeler, E. J., Otte, M. J., & Esslemont, R. J. (1994). Inter-relationships of periparturient diseases in dairy cows. Veterinary Record, 34(6), 129–132.

Peters, S. O., Hussain, T., Adenaike, A. S., Adeleke, M. A., De Donato, M., Hazzard, J., Babar, M. E., & Imumorin, I. G. (2018). Genetic diversity of bovine major histocompatibility complex class II DRB3 locus in cattle breeds from Asia compared to those from Africa and America. Journal of Genomics, 12(6), 88–97.

Prakash, C., Gaur, G. K., Pruthviraj, D. R., & Sahoo, N. R. (2019). Distribution analysis of single nucleotide polymorphisms related to feet and legs and their association with lameness in Vrindavani cattle. Tropical Animal Health and Production, 52, 851–858.

Ranjbar, M. M., Ataei, S., Nikbakht, G., & Golabdar, S. (2017). Analysis of variations, structures, and phylogenic characteristics of bovine leukocyte antigen DRB3 exon 2. Archives of Razi Institute, 72(3), 147–157.

Rupp, R., Hernandez, A., & Mallard, B. (2007). Association of bovine leukocyte antigen (BoLA) DRB3.2 with immune response, mastitis, and production and type traits in Canadian Holsteins. Journal Dairy Science, 90(2), 1029–1038.

Ruzina, M. N., Shtyfurko, T. A., Mohammad Abadi, M. R., Gendzhieva, O. B., Cedev, C., & Sulimova, G. E. (2010). Polimorfizm gena BoLA-DRB3 u krupnogo rogatogo skota mongol’skoj, kalmyckoj i jakutskoj porod [Polymorphism of the BoLA-DRB3 gene in the Mongolian, Kalmyk, and Yakut cattle breeds]. Russian Journal of Genetics, 46(4), 517–525 (in Russian).

Sharif, S., Mallard, B. A., Wilkie, B. N., Sargeant, J. M., Scott, H. M., Dekkers, J. C., & Leslie, K. E. (1998). Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle. Animal Genetics, 29, 185–193.

Singh, U., Deb, R., Alyethodi, R., Alex, R., Kumar, S., Chakraborty, S., Dhama, K., & Sharma, A. (2014). Molecular markers and their applications in cattle genetic research: A review. Biomarkers and Genomic Medicine, 6, 49–58.

Skorodumov, D. I. (2007). Mikrobiologicheskaja diagnostika nekrobakterioza [Microbiological diagnosis of necrobacillosis]. Veterinarija Sel’skohozjajstvennyh Zhivotnyh, 12, 21–25 (in Russian).

Sokolovsky, N. V., & Birukova, O. D. (2016). The influence of genotypical and paratypical factors on the incidence of limb in cows of Ukrainian black-and-white dairy breed. Animal Breeding and Genetics, 52, 114–119.

Sulimova, G. E. (2006). DNA markers in the study of gene pool of cattle breeds. Gene pools of farm animals: genetic resources of animal husbandry in Russia. Nauka, Moscow.

Sun, L., Song, Y., Riaz, H., Yang, L. (2013). Effect of BoLA-DRB3 exon 2 polymorphisms on lameness of Chinese Holstein cows. Molecular Biology Reports, 40(2), 1081–1086.

Suprovich, T., Karchevska, Т., Kolinchuk, R., & Mizyk, V. (2016). Vyiavlennia aleliv gena BoLA-DRB3.2, asocijovanih z nekrobakteriozom u koriv Ukrayinskoyi chorno-ryaboyi molochnoji porody [Determination of alleles of BoLA-DRB3.2 gene associated with necrobacteriosis of the cows of Ukrainian black-and-white dairy cattle]. Animal Breeding and Genetics, 51, 205–213 (in Ukrainian).

Suprovych, T. (2013). Doslidzhennja polimorfizmu gena BoLA-DRB3 u koriv spryjnjatlyvyh ta stijkyh do mastytiv [Study of gene polymorphisms BoLA-DRB3 cows susceptible and resistant to mastitis]. Tvarynnyctvo Ukrainy, 12, 14–19 (in Ukrainian).

Suprovych, T. M., Suprovych, M. P., & Kolinchuk, R. V. (2017). Naslidki “golshtinizaciyi” Ukrayinskoyi chorno-ryaboyi molochnoyi porodi za genom BoLA-DRB3.2 [Consequences of “holsteinization” of Ukrainian black-pied dairy breed by gene BoLA-DRB3.2]. Animal Breeding and Genetics, 54, 146–156 (in Ukrainian).

Swalve, H., Floren, C., Wensch-Dorendorf, M., Schöpke, K., Pijl, R., Wimmers, K., & Brenig, B. (2014). A study based on records taken at time of hoof trimming reveals a strong association between the IQ motif-containing GTPase-activiating protein 1 (IQGAP1) gene and sole hemorrhage in Holstein cattle. Journal of Dairy Science, 97 (1), 507–519.

Takeshima, S. N., Miyasaka, T., Matsumoto, Y., Xue, G., Diaz, V., Rogberg-Munoz, A., Giovambattista, G., Ortiz, M., Oltra, J., Kanemaki, M., Onuma, M., & Aida, Y. (2015). Assessment of biodiversity in Chilean cattle using the distribution of major histocompatibility complex class II BoLA-DRB3 allele. Tissue Antigens, 85(1), 35–44.

Takeshima, S. N., Miyasaka, T., Polata, M., Kikuya, M., Matsumoto, Y., Mingala, C. N., Villanueva, M. A., Salces, A. J., Onuma, M., & Aida, Y. (2014). The great diversity of major histocompatibility complex class II genes in Philippine native cattle. Meta Gene, 2, 176–190.

Valilou, R. H., Sarskanroud, M. R., Rafat, S. A., Ebrahimi, M., Firouzamandi, M., & Mohammadi, S. A. (2016). Association between footrot resistance and microsatellite polymorphisms of ovar-DRB1 and BMC5221 loci in Iranian Ghezel sheep. Revue de Medecine Veterinaire, 167(11–12), 316–322.

Van der Linde, C., De Jong, G., Koenen, E. P. C., & Eding, H. (2010). Claw health index for Dutch dairy cattle based on claw trimming and conformation data. Journal of Dairy Science, 93, 4883–4891.

Van der Spek, D., Van Arendonk, J. A. M., & Bovenhuis, H. (2015). Genome-wide association study for claw disorders and trimming status in dairy cattle. Journal of Dairy Science, 98(2), 1286–1295.

Van Eijk, M. J. T., Stewart-Haynes, J. A., & Lewin, H. A. (1992). Extensive polymorphism of the BoLA-DRB3 gene distinguished by PCR-RFLP. Animal Genetics, 23(6), 483–496.

Vinnikov, М. G., Melnik, R., Melnik, N. V., Samuylenko, А. Y., Grin, S. А. Klyukina, V., Svyatenko, M. S., Yartsev, S. D., & Khaustova, N. V. (2019). Nekrobakterioz i meroprijatija po ego preduprezhdeniju u vysokoproduktivnogo importnogo skota [Necrobacteriosis and measures to prevent it in highly productive imported livestock]. Veterinaria i Kormlenie, 3, 32–35 (in Russian).

Zhovnir, O. М., Gorbatiuk, O. I., Andriyashchuk, V. A., Ryzhenko, G. F., Tiutiun, S. M., Rudoi, A. V., & Kamenchuk, P. P. (2015). Monitoryng nekrobakteriozu, osnovnyj vydovyj spektr mikrobnyh asociacij za uchasti F. necrophorum ta specyfichni zasoby profilaktyky [Monitoring of necrobacillosis and species range of the most common microbial associations involving F. necrophorum]. Veterynarna Bіotehnologіja, 27, 112–121 (in Ukrainian).

How to Cite
Suprovych, T. M., Suprovych, M. P., Kolinchuk, R. V., Karchevska, T. M., Chornyi, I. O., & Kolodiy, V. A. (2020). Association of BoLA-DRB3.2 alleles with fusobacteriosis in cows . Regulatory Mechanisms in Biosystems, 11(2), 249-254.