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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Genetics</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Genetics</journal-title><trans-title-group xml:lang="ru"><trans-title>Генетика</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0016-6758</issn><issn publication-format="electronic">3034-5103</issn><publisher><publisher-name xml:lang="en">The Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">676596</article-id><article-id pub-id-type="doi">10.31857/S0016675824120079</article-id><article-id pub-id-type="edn">waawue</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>ГЕНЕТИКА ЖИВОТНЫХ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Evaulation of Polymorphism of the Immune System Genes <italic>TNF</italic> and <italic>TLR2</italic> in Cattle</article-title><trans-title-group xml:lang="ru"><trans-title>Оценка полиморфизма генов иммунной системы <italic>TNF</italic> и <italic>TLR2</italic> у крупного рогатого скота</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kalashnikova</surname><given-names>L. A.</given-names></name><name xml:lang="ru"><surname>Калашникова</surname><given-names>Л. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>ladnatehplem@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Bagal</surname><given-names>I. E.</given-names></name><name xml:lang="ru"><surname>Багаль</surname><given-names>И. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>ladnatehplem@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Murugina</surname><given-names>N. E.</given-names></name><name xml:lang="ru"><surname>Муругина</surname><given-names>Н. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>ladnatehplem@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kalashnikov</surname><given-names>V. E.</given-names></name><name xml:lang="ru"><surname>Калашников</surname><given-names>В. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>ladnatehplem@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Senina</surname><given-names>R. Yu.</given-names></name><name xml:lang="ru"><surname>Сенина</surname><given-names>Р. Ю.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>ladnatehplem@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">All-Russian Research Institute of Animal Breeding</institution></aff><aff><institution xml:lang="ru">Всероссийский научно-исследовательский институт племенного дела</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">National Research Center “Institute of Immunology”</institution></aff><aff><institution xml:lang="ru">Государственный научный центр “Институт иммунологии”</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2024-12-15" publication-format="electronic"><day>15</day><month>12</month><year>2024</year></pub-date><volume>60</volume><issue>12</issue><fpage>66</fpage><lpage>74</lpage><history><date date-type="received" iso-8601-date="2025-03-03"><day>03</day><month>03</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Russian Academy of Sciences</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Российская академия наук</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Russian Academy of Sciences</copyright-holder><copyright-holder xml:lang="ru">Российская академия наук</copyright-holder></permissions><self-uri xlink:href="https://transsyst.ru/0016-6758/article/view/676596">https://transsyst.ru/0016-6758/article/view/676596</self-uri><abstract xml:lang="en"><p>In this article the results of genotyping of tumor necrosis factor (TNF) and toll-like receptor 2 (TLR2) genes among 644 heads of cattle of six breeds belonging to four different genetic roots are presented. The Kholmogory and Holstein breeds of black-and-white root, the Ayrshire breed of red root, the Kostroma and Brown Swiss breed of brown root and the fawn Simmental breed were studied. The PCR-RFLP method was used to identify alleles and genotypes. Significant differences in allele frequency of the <italic>TNF</italic> and <italic>TLR</italic><italic>2</italic> genes were observed between breeds of different genetic roots (<italic>p</italic> &lt; 0.001) and between breeds of dairy and dairy-meat productivity (<italic>p</italic> &lt; 0.001). In five of the six cattle breeds studied, the predominance of the <italic>TLR</italic><italic>2</italic><italic><sup>T</sup></italic> allele was revealed. The highest frequency of the <italic>TLR</italic><italic>2</italic><italic><sup>T</sup></italic> allele (0.99) was found in the Ayrshire breed. The herd of Ayrshire cows is close to being monomorphic for the <italic>TLR</italic><italic>2</italic> gene, 98% of the animals have the homozygous <italic>TLR</italic><italic>2</italic><italic><sup>TT</sup></italic> genotype. A more uniform distribution of alleles and genotypes for the <italic>TLR</italic><italic>2</italic> gene was found in black-and-white animals: in Holstein cattle the average frequency of the <italic>TLR</italic><italic>2</italic><italic><sup>T</sup></italic> allele was 0.78, in Kholmogory cattle it was 0.83. The <italic>TLR</italic><italic>2</italic><italic><sup>TT</sup></italic> genotype was detected in the majority of Holstein (61%) and Kholmogory (69%) cows. The frequency of the <italic>TLR</italic><italic>2</italic><italic><sup>T</sup></italic> allele in the Simmental breed was 0.62, in the Kostroma breed – 0.67. In Simmental and Kostroma cows, the heterozygous <italic>TLR</italic><italic>2</italic><italic><sup>TG</sup></italic><sup> </sup>genotype is more common (54 and 47% respectively). A different picture of the distribution of allele and genotype frequencies was revealed in Brown Swiss animals. The <italic>TLR</italic><italic>2</italic><italic><sup>T</sup></italic> allele frequency averages 0.26. More than half of Brown Swiss cows (55%) are homozygous for <italic>TLR</italic><italic>2</italic><italic><sup>GG</sup></italic>. In all breeds, the <italic>TNF<sup>B</sup></italic> allele predominated with a frequency of occurrence ranging from 0.61 in Holstein cattle to 0.98 in the Brown Swiss breed. A high frequency of the <italic>TNF<sup>B</sup></italic> allele was found in the Kostroma (0.94), Ayrshire (0.885) and Simmental (0.80) breeds. In the Kholmogory breed, the average frequency of the <italic>TNF<sup>B</sup></italic> allele was 0.72. The highest frequency of the <italic>TNF<sup>BB</sup></italic> genotype was found in Brown Swiss herds (96%). The predominance of the homozygous <italic>TNF<sup>BB</sup></italic> genotype was revealed in Kholmogory (53%), Simmental (62%), Ayrshire (77%) and Kostroma cattle (87.5%). In Holstein cows, the majority of animals (53%) carry the heterozygous <italic>TNF</italic><italic><sup>АВ</sup></italic> genotype. In three breeds – Ayrshire, Kostroma and Brown Swiss, the TNF<sup>AA</sup> genotype was not detected.</p></abstract><trans-abstract xml:lang="ru"><p>Представлены результаты генотипирования генов фактора некроза опухоли (<italic>TNF</italic>) и толл-подобного рецептора 2 (<italic>TLR2</italic>) у 644 голов крупного рогатого скота шести пород, относящихся по происхождению к четырем разным генетическим корням. Исследованы холмогорская и голштинская породы черно-пестрого корня, айрширская порода красного корня, костромская и бурая швицкая породы бурого корня и палевая симментальская порода. Для выявления аллелей и генотипов использовали метод ПЦР-ПДРФ. Установлены достоверные различия частоты встречаемости аллелей генов <italic>TNF</italic> и <italic>TLR2</italic> между породами разных генетических корней (<italic>р</italic> &lt; 0.001) и между породами молочного и молочно-мясного направления продуктивности (<italic>р</italic> &lt; 0.001). У пяти пород скота из шести изученных по гену <italic>TLR2</italic> выявлено преобладание аллеля <italic>T</italic>, наиболее высокая его частота (0.99) установлена у айрширской породы. Стадо айрширских коров близко к мономорфному типу по гену <italic>TLR2</italic>, 98% животных имеют гомозиготный генотип <italic>TТ</italic>. Более равномерное распределение аллелей и генотипов по гену <italic>TLR2</italic> установлено у животных черно-пестрого корня: у голштинского скота средняя частота аллеля <italic>T</italic> составила 0.78, у холмогорского – 0.83. Генотип <italic>TТ</italic> выявлен у большинства голштинских (61%) и холмогорских (69%) коров. Частота аллеля <italic>T</italic> у симментальской породы составила 0.62, у костромской породы – 0.67. У симментальских и костромских коров чаще встречается гетерозиготный генотип <italic>TG</italic> (54 и 47% соответственно). Иная картина распределения частоты аллелей и генотипов выявлена у животных бурой швицкой породы. Частота аллеля <italic>T</italic><sup> </sup>составляет в среднем 0.26. Более половины коров бурой швицкой породы (55%) имеют гомозиготный генотип <italic>GG</italic>. У всех пород по гену <italic>TNF</italic> преобладал аллель В с частотой встречаемости от 0.61 у голштинского скота до 0.98 у бурой швицкой породы. Высокая частота аллеля <italic>В</italic><sup> </sup>установлена у костромской (0.94), айрширской (0.885) и симментальской (0.80) пород; у холмогорской породы выявлена средняя частота данного аллеля – 0.72. Наиболее высокая частота генотипа <italic>ВВ</italic> установлена в стадах бурой швицкой породы (96%). Выявлено преобладание гомозиготного генотипа <italic>ВВ</italic><sup> </sup>у холмогорского (53%), симментальского (62%), айрширского (77%) и костромского скота (87.5%). У голштинских коров большинство животных (53%) представлены гетерозиготным генотипом <italic>АВ</italic>. У трех пород – айрширской, костромской и бурой швицкой – не выявлен генотип <italic>АА</italic>.</p></trans-abstract><kwd-group xml:lang="en"><kwd>cattle</kwd><kwd>immune system genes</kwd><kwd>TNF</kwd><kwd>TLR2</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>крупный рогатый скот</kwd><kwd>гены иммунной системы</kwd><kwd>TNF</kwd><kwd>TLR2</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Российский научный фонд (проект)</institution></institution-wrap><institution-wrap><institution xml:lang="en">Russian Science Foundation (project)</institution></institution-wrap></funding-source><award-id>23-26-00235</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Bjelka M., Novák K. Association of TLR gene variants in a Czech Red Pied cattle population with reproductive traits // Vet. Immunol. Immunopathol. 2020. V. 220. doi: 10.1016/j.vetimm.2019.109997</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Elmagharaby M.M., El-Nahas A.F., Fathala M.M. et al. Association of toll-like receptors 2 and 6 polymorphism with clinical mastitis and production traits in Holstein cattle // Iranian J. Veter. Res. 2018. V. 19. № 3. P. 202–207.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Puerto M.A., Shepley E., Cue R.I. et al. The hidden cost of disease: I. Impact of the first incidence of mastitis on production and economic indicators of primiparous dairy cows // J. Dairy Sci. 2021. V. 104. № 7. P. 7932–7943. doi: 10.3168/jds.2020-19584</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Aghamohammadi M., Haine D., Kelton D.F. et al. Herd-level mastitis-associated costs on canadian dairy farms // Front. Veter. Sci. 2018. V. 5. doi: 10.3389/fvets.2018.00100</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Trinchieri G., Sher A. Cooperation of Toll-like receptor signals in innate immune defence // Nat. Rev. Immunol. 2007. V. 7. № 3. P. 179–190. doi:10.1038/nri2038</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>McGuire K., Jones M., Werling D. et al. Radiation hybrid mapping of all 10 characterized bovine Toll-like receptors // Anim. Genet. 2006. V. 37. № 1. P. 47–50.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Zhang L.P., Gan Q.F., Ma T.H. et al. Toll-like receptor 2 gene polymorphism and its relationship with SCS in dairy cattle // Anim. Biotechnol. 2009. V. 20. P. 87–95. doi: 10.1080/10495390902873096</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Takeda K., Akira S. Toll-like receptors in innate immunity // Int. Immunol. 2005. V. 17. № 1. P. 1–14. doi: 10.1093/intimm/dxh186</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity // Cell. 2006. V. 124. № 4. P. 783–801. doi: 10.1016/j.cell.2006.02.015</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Ozinsky A., Underhill D.M., Fontenot J.D. et al. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors // Proc. Natl Acad. Sci. USA. 2000. V. 97. № 25. P. 13766–13771. doi: 10.1073/pnas 250476497</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Inrning Huang J., Liu L., Wang H. et al. Variants and gene expression of the TLR2 gene and susceptibility to mastitis in cattle // Asian J. Anim. Veter. Adv. 2011. V. 6. P. 51–61. doi: 10.3923/ajava.2011.51.61</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Raufian P., Shodja Ghyas J., Jafari R. et al. Identification of genetic variation in two candidate genes of TLR2 and TNFα and its association with mastitis in Holstain Cattle // Res. Anim. Prod. (Sci. Res.). 2018. V. 8. P. 147–154. doi: 10.29252/rap.8.18.147</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Goldammer T., Zerbe H., Molenaar A. et al. Mastitis increases mammary mRNA abundance of β-defensin 5, toll-like-receptor 2 (TLR2), and TLR4 but not TLR9 in cattle // Clin. Diagn. Lab. Immunol. 2004. V. 11. № 1. P. 174–185. doi: 10.1128/CDLI.11.1.174-185.2004</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Sadana T., Singh R., Singh Sh. et al. Single nucleotide polymorphism of SLC11A1, CARD15, IFNG and TLR2 genes and their association with Mycobacterium avium subspecies paratuberculosis infection in native Indian cattle population // Indian J. Biotechnol. 2015. V. 14. P. 469–475.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Koets A., Santema W., Mertens H. et al. Susceptibility to paratuberculosis infection in cattle is associated with single nucleotide polymorphisms in Toll-like receptor 2 which modulate immune responses against Mycobacterium avium subspecies paratuberculosis // Prev. Veter. Med. 2010. V. 93. № 4. P. 305–315. doi: 10.1016/j.prevetmed.2009.11.008</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Bartens M.C., Gibson A.J., Etherington G.J. et al. Single Nucleotide polymorphisms in the bovine TLR2 extracellular domain contribute to breed and species-specific innate immune functionality // Front. Immunol. 2021. V. 12. doi: 10.3389/fimmu.2021.764390</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Bhaladhare A., Sharma D., Kumar A. et al. Single nucleotide polymorphisms in Toll-like receptor genes and case-control association studies with bovine tuberculosis // Veter. World. 2016. V. 9. № 5. doi: 10.14202/vetworld.2016.458-464</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Huang L.Y., Aliberti J., Leifer C.A. et al. Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is Toll-like receptor 2 dependent // J. Immunol. 2003. V. 171. № 3. P. 1441–1446. doi: 10.4049/jimmunol.171.3.1441</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Aggarwal B.B., Kohr W.J., Hass P.E. et al. Human tumor necrosis factor. Production, purification, and characterization // J. Biol. Chem. 1985. V. 260. № 4. P. 2345–2354.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Pennica D., Nedwin G.E., Hayflick J.S. et al. Human tumour necrosis factor: Precursor structure, expression and homology to lymphotoxin // Nature. 1984. V. 312 (5996). P. 724–729. doi: 10.1038/312724a0</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Agaba M., Kemp S.J., Barendse W., Teale A.J. Polymorphism at the bovine tumor necrosis factor alpha locus and assignment to BTA23 // Mamm. Genome. 1996. V. 7. P. 186−187. doi:10.1007/s003359900051</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Grosse W.M., Kappes S.M., Laegreid W.W. et al. Single nucleotide polymorphism (SNP) discovery and linkage mapping of bovine cytokine genes // Mamm. Genome. 1999. V. 10. № 11. P. 1062–1069. doi:10.1007/s003359901162</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Bannerman D.D. Pathogen-dependent induction of cytokines and other soluble inflammatory mediators during intramammary infection of dairy cows // J. Anim. Sci. 2009. V. 87 (13 Suppl.). P. 10–25. doi: 10.2527/jas.2008-1187</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Bradley J.R. TNF-mediated inflammatory disease // J. Pathol. 2008. V. 214. № 2. P. 149–160. doi: 10.1002/path.2287</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Raoofian P., Shoja J., Moghadam G.H., Javanmard A. Association investigation and gene expression in genotypes TNFα with somatic cell score in Holstein Dairy cattle // Iranian J. Veter. Clin. Sci. Fall. 2018. V. 12. № 2. P. 59–134.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Wojdak-Maksymiec K., Szyda J., Strabel T. Parity-dependent association between TNF-α and LTF gene polymorphisms and clinical mastitis in dairy cattle // BMC Vet. Res. 2013. V. 9. doi: 10.1186/1746-6148-9-114</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Xu A.J., Liu X.L., Guo J.Z., Xia Z. Polymorphism of bovine TNF-a gene and its association with mastitis in Chinese Holstein cows // Yi Chuan. 2010. V. 32. № 9. P. 929–934.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Bojarojć-Nosowicz B., Kaczmarczyk E., Stachura A., 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 // Polish J. Vet. Sci. 2011. V. 14. № 4. P. 671–673. doi: 10.2478/v10181-011-0101-0</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Lendez P.A., Passucci J.A., Poli M.A. et al. Association of TNF-a gene promoter region polymorphisms in bovine leukemia virus (BLV)-infected cattle with different proviral loads // Arch. of Virology. 2015. V. 160. № 8. P. 2001–2007. doi: 10.1007/s00705-015-2448-5</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Cheng Y., Huang C., Tsai H. Relationship of bovine TNF-α gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle // J. Vet. Med. Sci. 2016. V. 78. № 5. P. 727–732. doi:10.1292/jvms.15-0506</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Kawasaki Y., Aoki Y., Magata F. et al. The effect of single nucleotide polymorphisms in the tumor necrosis factor-α gene on reproductive performance and immune function in dairy cattle // J. Reprod. and Development. 2014. V. 60. № 3. P. 173–178. doi: 10.1262/jrd.2013-140</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Bimenova Zh.Zh., Makashev Y.K., Turyspayeva Sh.D. et al. The effect of the TNF-α gene alleles in Holstein cows on reproductive function // J. Pharmaceutical Sci. and Res. 2018. V. 10. № 4. P. 903–906.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Kahl S., Proszkowiec Wegla M.K., Connor E.E., Elsasser T.H. Association of tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphisms with TNF-alpha response to endotoxin (LPS) in calves // J. Animal Sci. Abstract. 2008. V. 86. P. 195.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Prebavathy T., Thanislass J., Dhanammal L. et al. Association between SNPs in TLR2 gene segment corresponding to LRR functional domain of TLR2 receptor and bovine mastitis // Asian J. Animal Sci. 2015. V. 9. P. 45–56.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Oner Y., Ata N., Karabaş M., Yilmaz O. Investigation of TLR2 -EcoRV, NOD2- BsaHI ve IFNγ- HphI allele frequency distribution among Turkish Native Cattle Breeds // Turkish J. Agriculture. Food Sci. and Technol. 2022. V. 10. № 6. P. 992–996. doi: 10.24925/turjaf.v10i6.992-996.4701</mixed-citation></ref></ref-list></back></article>
