ivmМеждународный вестник ветеринарииInternational Journal of Veterinary Medicine2072-2419SpbGUVM Publishing House10.52419/issn2072-2419.2024.4.518ivm-1562Research ArticleАКУШЕРСТВО, ГИНЕКОЛОГИЯOBSTETRICS, GYNECOLOGYПопуляционно-генетическая характеристика крупного рогатого скота по гену MC4R (рецептор Меланокортина 4)POPULATION-GENETIC CHARACTERISTICS OF CATTLE BY THE MC4R (MELANOCORTIN 4 RECEPTOR) GENEhttps://orcid.org/0000-0003-1184-3188СафинаН. Ю.SafinaN. Yu.

Сафина Н.Ю. – канд. биол. наук, ст. науч. сотр. 

Safina N.Yu. – Candidate of Biological Sciences, Senior Researcher

natysafina@gmail.comhttps://orcid.org/0000-0002-8086-1788КрупинЕ. О.KrupinE. O.

Крупин Е.О. – д-р ветеринар. наук, вед. науч. сотр. 

Krupin E.O. – Doctor of Veterinarian Sciences, Leading Researcher

Татарский научно-исследовательский институт сельского хозяйства ФИЦ КазНЦ РАНРоссияTatar Scientific Research Institute of Agriculture “Kazan Scientific Center of Russia Academy of Sciences”Russian Federation20242001202504518527Copyright © Сафина Н.Ю., Крупин Е.О., 20242024Сафина Н.Ю., Крупин Е.О.Safina N.Y., Krupin E.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vetjournal.spbguvm.ru/jour/article/view/1562

Целью работы являлось дать популяционно-генетическую характеристику крупного рогатого скота татарстанского типа холмогорской породы Республики Татарстан по гену MC4R (рецептор меланокортина 4). В результате проведенного генотипирования методом ПЦРПДРФ по локусу гена MC4R - HpySE526I установлено 2 аллеля и 3 генотипа. Частота встречаемости аллелей: С – 0,434 и G – 0,566; генотипов CC – 20,9; CG – 45,0 и GG – 34.1%. Тест хи-квадрат (χ²) показал, что изучаемая популяция находится в генетическом равновесии. Отрицательный коэффициент Селендера (D) указывает на аутбридинг у популяции. Мониторинг работ по изучению полиморфизма гена 1069C˃G (Leu286Val) указывает на значительную вариабельность соотношения полиморфных форм гена MC4R в различных популяция крупного рогатого скота в зависимости от его географической и породной принадлежности. В среднем по всем рассматриваемым породам крупного рогатого скота мировых популяций соотношение аллелей гена MC4R – 0,537 и 0,463 для аллеля C и G соответственно. Соотношение генотипов CC, CG и GG гена MC4R по всем анализируемым популяциям крупного рогатого скота в среднем составило 32,5; 42,3 и 25,2 %. Анализ, проведенный с использованием данных зарубежных ученых, и результатов, полученных в нашем исследовании, характеризует мировые популяции крупного рогатого скота как генетически биоразнообразные, обладающие генетическим полиморфизмом по гену MC4R с высокой степенью гетерозиготности. Исследование выполнено в рамках государственного задания, регистрационный номер 122011800138-7.

The aim of the work was to provide a population genetic characteristic of the Kholmogorsky breed of the Tatarstan type of the Republic of Tatarstan for the MC4R gene (melanocortin 4 receptor). As a result of genotyping by the PCR-RFLP method for the MC4R - HpySE526I gene locus, 2 alleles and 3 genotypes were identified. The frequency of alleles: C - 0.434 and G - 0.566; and frequency of genotypes: CC - 20.9, CG - 45.0 and GG - 34.1%. The chi-square test (χ²) showed that the studied population the Hardy–Weinberg genetic equilibrium is not disturbed. A negative Selender coefficient (D) indicates outbreeding in the population. Monitoring of works on studying the polymorphism of the gene 1069C˃G (Leu286Val) shows a significant variability in the ratio of polymorphic forms of the MC4R gene in different cattle populations depending on their geographic and breed affiliation. On average, for all the considered cattle breeds of the world populations, the frequency of alleles of the MC4R gene is 0.537 and 0.463 for the allele C and G, respectively. The ratio of the CC, CG and GG genotypes of the MC4R gene for all analyzed cattle populations averaged 32.5, 42.3 and 25.2%. The analysis carried out using the data of foreign scientists and the results obtained in our study characterizes the world populations of cattle as genetically biodiverse, possessing genetic polymorphism for the MC4R gene with a high degree of heterozygosity. This research was supported by FASO Russia project, registration number 122011800138-7.

геналлельгетерозиготностьбиоразнообразиеполиморфизмMC4Rрецептор меланокортина 4genealleleheterozygositybiodiversitypolymorphismMC4Rmelanocortin 4 receptorСтатья подготовлена в рамках государственного задания: Эколого-генетические подходы к созданию и сохранению ресурсов растений и животных, расширению их адаптивного потенциала и биоразнообразия, разработка сберегающих агротехнологий с целью повышения устойчивости производства высококачественной продукции, достижения безопасности для здоровья человека и окружающей среды. Номер регистрации: 122011800138-7.This research was supported by the Ecological and genetic approaches to the creation and conservation of plant and animal resources, the expansion of their adaptive potential and biodiversity, the development of conservation agrotechnologies to increase the sustainability of high-quality products, achieve safety for human health and the environment. FASO Russia project. Registration number: 122011800138-7.ReferencesSafina N. Dairy productivity of Holstein cattle with different genotypes of the paraoxonase-1 (PON1) gene / N. Safina, Sh. Shakirov, E. Gaynutdinova et al. // E3S Web of Conferences. – 2021. Vol. 282. – P. 02007. DOI 10.1051/e3sconf/202128202007Safina N., Shakirov Sh., Gaynutdinova E., Fattakhova Z. Dairy productivity of Holstein cattle with different genotypes of the paraoxonase-1 (PON1) gene // E3S Web of Conferences. 2021. 282:02007. DOI 10.1051/e3sconf/202128202007Safina N.Polymorphism of the glutathioneperoxidase-1 gene (GPX-1 g. 189 T/C) and biochemical parameters of the blood serum of Holstein cattle / N. Safina, Sh. Shakirov, E. Gaynutdinova et al. // E3S web of conferences. – 2023. – Vol. 462. – P. 01018. DOI 10.1051/e3sconf/202346201018Safina N., Shakirov Sh., Gaynutdinova E., Mukhanina E., Shayakhmetova L., Bagavieva E., Fattakhova Z., Akhmetov T., Zagidullin L., Haertdinov R. Polymorphism of the glutathioneperoxidase-1 gene (GPX-1 g. 189 T/C) and biochemical parameters of the blood serum of Holstein cattle // E3S web of conferences. 2023. 462:01018. DOI 10.1051/e3sconf/202346201018Gantz I. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor / I. Gantz, H. Miwa, Y. Konda et al. // J. Biol. Chem. – 1993. – Vol. 268 (20). – P. 15174–15179.Gantz I., Miwa H., Konda Y., Shimoto Y., Tashiro T., Watson S.J., DelValle J., Yama da T. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor // J. Biol. Chem. 1993. 268 (20):15174–15179.Ju S.H. Understanding melanocortin-4 receptor control of neuronal circuits: toward novel therapeutics for obesity syndrome / S.H. Ju, G.-B. Cho, J.-W. Sohn et al. // Pharmacol. Res. – 2018. – Vol. 129. – P. 10–19. DOI: 10.1016/j.phrs.2018.01.004Ju S.H., Cho G.-B., Sohn J.-W. Understanding melanocortin-4 receptor control of neuronal circuits: toward novel therapeutics for obesity syndrome // Pharmacol. Res. 2018. 129:10–19. DOI: 10.1016/j.phrs.2018.01.004Cone R.D. Anatomy and regulation of the central melanocortin system / R.D. Cone // Nat. Neurosci. – 2005. – Vol. 8. – P. 571–578. DOI 10.1038/nn1455Cone R.D. Anatomy and regulation of the central melanocortin system // Nat. Neurosci. 2005. 8:571–578. DOI 10.1038/nn1455Tao Y.-X. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology / Y.-X. Tao // Endocr. Rev. – 2010. – Vol. 31(4). – P. 506–543. DOI: 10.1210/er.2009-0037Tao Y.-X. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology // Endocr. Rev. 2010. 31(4):506–543. DOI: 10.1210/er.2009-0037Ardicli S., Alpay F. The effects of MC4R and CACNA2D1 gene polymorphisms on carcass traits and marbling score in Turkish native cattle breeds and their crossbreds with the Holstein-Friesians / S. Ardicli, F. Alpay // Genetika. – 2023. – Vol. 55(2). – P. 655-672 DOI 10.2298/GENSR2302655AArdicli S., Alpay F. The effects of MC4R and CACNA2D1 gene polymorphisms on carcass traits and marbling score in Turkish native cattle breeds and their crossbreds with the Holstein-Friesians // Genetika. 2023. 55 (2):655-672 DOI 10.2298/GENSR2302655ALubrano-Berthelier C. The human MC4R promoter: characterization and role in obesity / C. Lubrano-Berthelier, M. Cavazos, C. Le Stunff et al. // Diabetes. – 2003. – Vol. 52 (12). – P. 2996–3000. DOI: 10.2337/diabetes.52.12.2996Lubrano-Berthelier C., Cavazos M., Le Stunff C., Haas K., Shapiro A., Zhang S., Bougneres P., Vaisse C. The human MC4R promoter: characterization and role in obesity // Diabetes. 2003. 52(12):2996–3000. DOI: 10.2337/diabetes.52.12.2996Prihandini P.W., Maharani D. Melanocortin-4 Receptor (MC4R) Gene as the Main Gene for Rapid Growth Selection in Beef Cattle / P.W. Prihandini, D. Maharani // WARTAZOA. – 2019. – Vol. 29(2). – P. 085-096 DOI 10.14334/wartazoa.v29i2.1955Prihandini P.W., Maharani D. Melanocortin-4 Receptor (MC4R) Gene as the Main Gene for Rapid Growth Selection in Beef Cattle // WARTAZOA. 2019. 29(2):085-096 DOI 10.14334/wartazoa. v29i2.1955Zhang, Y. α-Melanocyte-stimulating hormone prevents glutamate excitotoxicity in developing chicken retina via MC4Rmediated down-regulation of microRNA19 / Y. Zhang, Q. Bo, W. Wu et al. // Sci. Rep. – 2015. – Vol. 5. – P. 15812. https://doi.org/10.1038/srep15812Zhang Y., Bo Q., Wu W., Xu C., Yu G., Ma S., Yang Q., Cao Y., Han Q., Ru Y. αMelanocyte-stimulating hormone prevents glutamate excitotoxicity in developing chicken retina via MC4R-mediated downregulation of microRNA-19 // Sci. Rep. 2015. 5:15812. https://doi.org/10.1038/srep15812Liu G.L. Molecular screening of MC4R gene and association with fat traits in pig resource family / G.L. Liu, S.W. Jiang, Y.Z. Xiong et al. // Yi Chuan Xue Bao, Chinese. – 2002. – Vol. 29(6). – P. 497–501.Liu G.L., Jiang S.W., Xiong Y.Z., Zheng R., Qu Y.C. Molecular screening of MC4R gene and association with fat traits in pig resource family // Yi Chuan Xue Bao, Chinese. 2002. 29(6):497–501.Marie L.S. A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors / L.S. Marie, G.I. Miura, D.J. Marsh et al. // Proc. Natl. Acad. Sci. – 2000. – Vol. 97(22). – P. 12339–12344. doi: 10.1073/pnas.220409497Marie L.S., Miura G.I., Marsh D.J., Yagaloff K., Palmiter R.D. A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors // Proc. Natl. Acad. Sci. 2000. 97(22):12339–12344. doi: 10.1073/pnas.220409497Haupt A. Impact of variation near MC4R on whole-body fat distribution, liver fat, and weight loss / A. Haupt, C. Thamer, M. Heni et al. // Obesity. – 2009. – Vol. 17(10). – P. 1942–1945. DOI: 10.1038/oby.2009.233Haupt A., Thamer C., Heni M., Tschritter O., Machann J., Schick F., Machicao F., Häring H., Staiger H., Fritsche A. Impact of variation near MC4R on whole-body fat distribution, liver fat, and weight loss // Obesity. 2009. 17(10):1942–1945. DOI: 10.1038/oby.2009.233Seong J. Identification and analysis of MC4R polymorphisms and their association with economic traits of Korean cattle (Hanwoo) / J. Seong, D.S. Suh, K.D. Park et al. // Mol Biol Rep. – 2012. – Vol. 39(4). – P. 3597-3601. DOI: 10.1007/s11033-011-1133-3Seong J., Suh D.S., Park K.D., Lee H.K., Kong H.S. Identification and analysis of MC4R polymorphisms and their association with economic traits of Korean cattle (Hanwoo) // Mol Biol Rep. 2012. 39(4):3597-3601. DOI: 10.1007/s11033-011-1133-3Haegeman A. Bovine melanocortin receptor 4: cdna sequence, polymorphisms and mapping / A. Haegeman, F. Coopman, K. Jacobs et al. // Anim Genet. – 2001. – Vol. 32(4). – P. 189–192.Haegeman A., Coopman F., Jacobs K., Mattheeuws M., van Zeveren A., Peelman L. Bovine melanocortin receptor 4: cdna sequence, polymorphisms and mapping // Anim Genet. 2001. 32(4):189–192.Thue T.D. A SNP in the cattle MC4R gene is used to map MC4R to BTA 24 / T.D. Thue, S.M. Schmutz, F.C. Buchanan // Anim Genet. – 2001. – Vol. 32(6). – P. 390–391. DOI: 10.1046/j.1365-2052.2001.0781b.xThue T.D., Schmutz S.M., Buchanan F.C. A SNP in the cattle MC4R gene is used to map MC4R to BTA 24 // Anim Genet. 2001. 32(6):390–391. DOI: 10.1046/j.1365-2052.2001.0781b.xLiu G. The genetic polymorphisms of melanocortin-4 receptor gene are associated with carcass quality traits in a Chinese indigenous beef cattle breed / G. Liu, S. Raza, L. Zhou et al. // Research in Veterinary Science. – 2020. – Vol. 132. – P. 202-206. DOI 10.1016/j.rvsc.2020.06.011.Liu G., Raza S., Zhou L., El-Aziz A., Sabek A., Shoorei H., Amjadi M., Gui L. The genetic polymorphisms of melanocortin4 receptor gene are associated with carcass quality traits in a Chinese indigenous beef cattle breed // Research in Veterinary Science. 2020. 132:202-206. DOI 10.1016/j.rvsc.2020.06.011.Lee Y. A C1069G SNP of the MC4R gene and its association with economic traits in Korean native cattle (brown, brindle, and black) / Y. Lee, S. Park, H. Kim et al. // Electronic Journal of Biotechnology, North America. – 2013. – Vol. 16(5). DOI: 10.2225/vol16-issue5-fulltext-5Lee Y., Park S., Kim H., Lee S., Kim J., Lee H., Jeong D., Lee S. A C1069G SNP of the MC4R gene and its association with economic traits in Korean native cattle (brown, brindle, and black) // Electronic Journal of Biotechnology, North America. 2013. 16(5): DOI: 10.2225/vol16-issue5-fulltext-5Liu H. Association of MC4R gene variants with carcass and meat quality traits in Qinchuan cattle / H. Liu, W. Tian, L. Zan et al. // African Journal of Biotechnology. – 2009. – Vol. 8(15). – P. 3666-3671. DOI: 10.5897/AJB09.406Liu H., Tian W., Zan L., Wang H., Cui H. Association of MC4R gene variants with carcass and meat quality traits in Qinchuan cattle // African Journal of Biotechnology. 2009. 8(15):3666-3671. DOI: 10.5897/AJB09.406Polini B. Prevalence of mutations in LEP, LEPR, and MC4R genes in individuals with severe obesity / B. Polini, P.E. Maltese, I.D. Ciondolo // Genet. Mol. Res. – 2016. – Vol. 15(3). – P. 201-209. DOI: 10.4238/gmr.15038718Polini B., Maltese P.E., Ciondolo I.D. Prevalence of mutations in LEP, LEPR, and MC4R genes in individuals with severe obesity // Genet. Mol. Res. 2016. 15(3):201-209. DOI: 10.4238/gmr.15038718Бальников А.А. Возможности маркерной селекции при оценке мясооткормочной продуктивности свиней / А.А. Бальников, Ю.С. Казутова, Е.С. Гридюшко и др. // Наше сельское хозяйство. – 2022. – № 4(276). – С. 74-82.Balnikov A.A., Kazutova Yu.S., Gridyushko E.S., Mikhailova M.E., Romanishko E.L. Possibilities of marker selection in assessing the meat-fattening productivity of pigs // Our agriculture. 2022. 4(276): 74-82.Курносова О.В. ДНК-маркеры продуктивности свиноматок / О.В. Курносова, Г.В. Максимов, А.Г. Максимов // Свиноводство. – 2019. – № 3. – С. 45-48.Kurnosova O.V., Maksimov G.V., Maksimova A.G. DNA markers of sow productivity // Pigbreeding. 2019. 3:45-48.Мельникова Е.Е. Влияние генотипов по IGF2, CCKAR и MC4R на фенотипические показатели и племенную ценность свиней по хозяйственно полезным признакам / Е.Е. Мельникова, Н.В. Бардуков, М.С. Форнара и др. // Сельскохозяйственная биология. – 2018. – Т. 53, № 4. – С. 723-734. – DOI 10.15389/agrobiology.2018.4.723rus.Melnikova E.E., Bardukov N.V., Fornara M.S., Kostyunina O.V., Sermyagin A.A., Zaitsev A.M., Zinovieva N.A. Effects of genotypes for IGF2, CCKAR and MC4R on the phenotypic estimations and breeding values for productive traits in pigs // Agricultural Biology. 2018. 53(4):723-734. DOI 10.15389/agrobiology.2018.4.723rus.Сердюк Г.Н. Полиморфизм генарецептора меланокортина MC4R у свиней различных пород / Г.Н. Сердюк // Генетика и разведение животных. – 2018. – № 3. – С. 27-31. DOI 10.31043/2410-2733-2018-3-27-31.Serdyuk G. Polymorphism of the MC4R melanocortin receptor gene in pigs of various breeds // Genetics and breeding of animals. 2018. 3:27-31. DOI 10.31043/2410-2733-2018-3-27-31.Huang M. Polymorphisms in MC4R gene and correlations with economic traits in cattle / M. Huang, X. Gao, J.Y. Li et al. // Mol Biol Rep. – 2010. – Vol. 37. – P. 3941–3944. DOI 10.1007/s11033-010-0051-0Huang M., Gao X., Li J.Y., Ren H.Y., Chen J.B., Xu S.Z. Polymorphisms in MC4R gene and correlations with economic traits in cattle // Mol Biol Rep. 2010. 37:3941–3944. DOI 10.1007/s11033-010-0051-0Zhang C.L. Association of a missense mutation of the MC4R gene with growth traits in cattle (Brief report) / C.L. Zhang, H. Chen, Y.H. Wang et al. // Arch. Anim. Breed. – 2006. – Vol. 49(5). – P. 515-516. https://doi.org/10.5194/aab-49-515-2006Zhang C.L., Chen H., Wang Y.H., Lan X.Y., Zhang L., Zhang A.L., Zhang R.F. Association of a missense mutation of the MC4R gene with growth traits in cattle (Brief report) // Arch. Anim. Breed. 2006. 49 (5):515-516. https://doi.org/10.5194/aab-49-515-2006Fadholly A. Profile of Melanocortin-4 Receptor and Myogenic Factor 5 Genes in Pasundan Beef Cattle / A. Fadholly, E. Margawati, A. Ibrahim et al. // Pakistan J. Zool. – 2024. – P. 1-6. DOI 10.17582/journal.pjz/20230310070334Fadholly A., Margawati E., Ibrahim A., Putra W. Profile of Melanocortin-4 Receptor and Myogenic Factor 5 Genes in Pasundan Beef Cattle // Pakistan J. Zool. 2024. 1-6. DOI 10.17582/journal.pjz/20230310070334Maharani D. Identification of MC4R gene and its association with body weight and body size in Kebumen Ongole Grade cattle / D. Maharani, A. Fathoni, S. Sumadi et al. // Journal of the Indonesian Tropical Animal Agriculture. – 2018. – Vol. 43(2). – P. 87-93. https://doi.org/10.14710/jitaa.43.2.87-93Maharani D., Fathoni A., Sumadi S., Hartatik T., and Khusnudin M., Identification of MC4R gene and its association with body weight and body size in Kebumen Ongole Grade cattle // Journal of the Indonesian Tropical Animal Agriculture. 2018. 43(2):87-93. https://doi.org/10.14710/jitaa.43.2.87-93

The authors declare that there are no conflicts of interest present.