ecodagЮг России: экология, развитиеSouth of Russia: ecology, development1992-10982413-0958State Institute of Applied Ecology of the Republic of Dagestan10.18470/1992-1098-2025-4-12ecodag-3579Research ArticleБИОЛОГИЧЕСКИЕ РЕСУРСЫBIOLOGICAL RESOURCESАллелофонд гена DRB1 OLA у овец различных породAllele pool of the DRB1 OLA gene in sheep of different breedshttps://orcid.org/0000-0002-1747-2800ДевришовД. А.DevrishovD. A.

Давудай А. Девришов

Москва

Davuday A. Devrishov

Moscow

https://orcid.org/0000-0001-9895-8046МарзановаС. Н.MarzanovaS. N.

Саида Н. Марзанова, кандидат биологических наук, доцент, доцент кафедры иммунологии и биотехнологии 

109472 г. Москва, ул. Академика Скрябина, 23.  Тел. +79268137147

Saida N. Marzanova, PhD (Biology), Associate Professor, Department of Immunology and Biotechnology

23 Academika Skryabin St,  Moscow, 109472.

Tel. +79268137147 

s.marzanova@mail.ruhttps://orcid.org/0009-0008-7536-1325ЖучковВ. А.ZhuchkovV. A.

Владислав А. Жучков

Москва

Vladislav A. Zhuchkov

Moscow

https://orcid.org/0000-0003-0708-6196МарзановН. С.MarzanovN. S.

Нурбий С. Марзанов

Москва

Nurbiy S. Marzanov

Moscow

https://orcid.org/0000-0002-3678-9926НиколаеваЕ. А.NikolaevaE. A.

Елизавета А. Николаева

Москва

Elizaveta A. Nikolaeva

Moscow

https://orcid.org/0000-0003-0427-8977ФатаховК. Ф.FatakhovK. F.

Курбан Ф. Фатахов

Москва

Kurban F. Fatakhov

Moscow

https://orcid.org/0000-0002-8820-5507ЕсенгалиевК. Г.YesengalievK. G.

Кайрлы Г. Есенгалиев

Уральск

Kairly G. Yesengaliev

Uralsk

https://orcid.org/0000-0002-3178-3277ДавлетоваА. М.DavletovaA. M.

Айнур М. Давлетова

Уральск

Ainur M. Davletova

Uralsk

https://orcid.org/0009-0003-2168-9708НысановЕ. С.NysanovE. S.

Ерсаин С. Нысанов

Уральск

Ersain S. Nysanov

Uralsk

Московская государственная академия ветеринарной медицины и биотехнологии – МВА имени К. И. СкрябинаK.I. Skhryabin Moscow State Academy of Veterinary Medicine and Biotechnology – MVA by K.I. SkryabinЗападно‐Казахстанский инновационно‐технологический университетWest Kazakhstan Innovation and Technology UniversityЗападно‐Казахстанская научно‐исследовательская ветеринарная станция – филиал Товарищества с ограниченной ответственностью «Казахский научно‐исследовательский ветеринарный институт»West Kazakhstan Scientific Veterinary Station branch of the Kazakh Scientific Research Veterinary Institute LLP202530012026204129‐137Copyright © Девришов Д.А., Марзанова С.Н., Жучков В.А., Марзанов Н.С., Николаева Е.А., Фатахов К.Ф., Есенгалиев К.Г., Давлетова А.М., Нысанов Е.С., 20262026Девришов Д.А., Марзанова С.Н., Жучков В.А., Марзанов Н.С., Николаева Е.А., Фатахов К.Ф., Есенгалиев К.Г., Давлетова А.М., Нысанов Е.С.Devrishov D.A., Marzanova S.N., Zhuchkov V.A., Marzanov N.S., Nikolaeva E.A., Fatakhov K.F., Yesengaliev K.G., Davletova A.M., Nysanov E.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ecodag.elpub.ru/ugro/article/view/3579Цель

Цель: проведение комплексного анализа вариабельности DRB1 локуса OLA, для установления уровня полиморфизма в исследуемых популяциях и породах овец, разводимых в различных условиях среды. Материал и методы включали оценку генетической дифференциации пород из России (дагестанская горная, дорпер, романовская, суффолк) и Казахстана (акжаикская). Популяции овец романовской породы были из Ярославской области, помеси эдильбаевская х калмыцкая – из Калмыкии. Расшифровку нуклеотидной последовательности ДНК осуществляли у 246 животных. Секвенирование проводили по Сэнгеру с последующим биоинформационным анализом. Статистическую обработку данных выполняли при помощи программ Microsoft Excel 2023, GenAlEx.

Результаты показали, что межпопуляционная вариация (Frt = 0,008, p = 0,005) объясняла 0,76 % дисперсии, тогда как различия между группами (Fsr = 0,044, p = 0,001) составляли 4,28 %. Отрицательное значение Fis (‐0,030, p = 0,997) свидетельствовало об избытке гетерозигот. Оценка потока генов (Nm = 4,58) подтвердила умеренный уровень миграции. У исследуемых популяций сохранялась избыточность аллелей с высокими уровнями гетерозиготности. Был отмечен статистически значимый уровень дифференциации популяций (Fst=5,2 %, p<0,001). 

Заключение

Заключение: аллелофонд гена DRB1 OLA показал типичную структуру с доминированием индивидуальной изменчивости исследованных популяций овец (95 %). В каждой породе присутствовали аллели, не встречающиеся у других. Исключением были популяции 3 и 9 в силу их малой выборки (n ≤ 10) ограничивающей возможность корректной статистической обработки и достоверного выделения уникальных аллелей. 

The objective was to conduct a comprehensive analysis of the variability of the DRB1 locus OLA, to establish the level of polymorphism in the populations and breeds of sheep studied bred in different environmental conditions.

Material and methods included an assessment of the genetic differentiation of breeds from Russia (Dagestan Mountain, Dorper, Romanov, Suffolk) and one from the Republic of Kazakhstan (Akzhaik). The Romanov sheep populations were from farms in the Yaroslavl region and the Edilbaevskaya x Kalmyk crossbreeds were from Kalmykia (Russia). The decoding of the nucleotide sequence of DNA was carried out in 246 animals. Sequencing was carried out according to Sanger, followed by the use of bioinformatics analysis procedures. Statistical data processing was carried out using Microsoft Excel 2023, GenAlEx programs. The results showed that the between‐population variation (Frt = 0.008, p = 0.005) explained only 0.76 % of the variance, while the differences between the groups (Fsr = 0.044, p = 0.001) were 4.28 %. The negative Fis value (‐0.030, p = 0.997) indicated an excess of heterozygotes. The gene flow assessment (Nm = 4.58) confirmed a moderate level of migration. All the studied populations retained an excess of alleles with high levels of heterozygosity. A statistically significant level of population differentiation was noted (Fst = 5.2 %, p < 0.001).

The DRB1 OLA gene allele pool showed a typical structure with a predominance of individual variability in the sheep populations studied (95 %). Each breed contained alleles not found in others. Populations 3 and 9 were an exception owing to their small sample size (n ≤ 10), which limited the possibility of accurate statistical analysis and reliable identification of unique alleles.

ОвцыпородыгенотипгеналлельDRB1OLAпаразитозыSheepbreedsgenotypegenealleleDRB1OLAparasitosesИсследование выполнено за счет гранта Российского научного фонда № 24‐26‐00197 (https://rscf.ru/project/24‐26‐00197/).The study was supported by Russian Science Foundation grant No. 24‐26‐00197 (https://rscf.ru/project/24‐26‐00197/).ReferencesDavies G., Stear M.J., Benothman M., Abuagob O., Kerr A., Mitchell S., Bishop S.C. Quantitative trait loci associated with parasitic infection in Scottish blackface sheep // Heredity (Edinb). 2006. V. 96. N 3. P. 252–258. https://doi.org/10.1038/sj.hdy.6800788.Davies G., Stear M.J., Benothman M., Abuagob O., Kerr A., Mitchell S., Bishop S.C. Quantitative trait loci associated with parasitic infection in Scottish blackface sheep. Heredity (Edinb), 2006, vol. 96, no. 3, pp. 252–258. https://doi.org/10.1038/sj.hdy.6800788Vasoya D., Oliveira P. S., Muriel L.A., Tzelos T., Vrettou Ch., Morrison W.I., Ferreira de Miranda Santos I.K., Connelley T. High throughput analysis of MHC‐I and MHC‐DR diversity of Brazilian cattle populations // HLA. 2021. V. 98. N 2. P. 93–113. https://doi.org/10.1111/tan.14339Vasoya D., Oliveira P.S., Muriel L.A., Tzelos T., Vrettou Ch., Morrison W.I., Ferreira de Miranda Santos I.K., Connelley T. High throughput analysis of MHC‐I and MHC‐DR diversity of Brazilian cattle populations. HLA, 2021, vol. 98, no. 2, pp. 93–113. https://doi.org/10.1111/tan.14339Vasoya D., Connelley T., Tzelos T., Todd H., Ballingall K.T. Large scale transcriptional analysis of MHC class I haplotype diversity in sheep // HLA. 2024. V. 103. N 2. Article id: e15356. https://doi.org/10.1111/tan.15356Vasoya D., Connelley T., Tzelos T., Todd H., Ballingall K.T. Large scale transcriptional analysis of MHC class I haplotype diversity in sheep. HLA, 2024, vol. 103, no. 2, article id: e15356. https://doi.org/10.1111/tan.15356Марзанова С.Н., Фатахов К.Ф., Девришов Д.А., Марзанов Н.С. Связь локусов главного комплекса гистосовместимости у овец (OLA) с резистентностью и восприимчивостью их к паразитозам // Ветеринария. 2024. N 7. C. 28‒33. https://doi.org/10.30896/00424846.2024.27.7.28‐33Marzanova S.N., Fatakhov K.F., Devrishova D.A., Marzanov N.S. Relationship of loci of the major histocompatibility complex in sheep (OLA) with their resistence and susceptibility to parasitoses.Veterinary science, 2024. no. 7. pp. 28‒33. (In Russian) https://doi.org/10.30896/0042‐4846.2024.27.7.28‐33Марзанова С.Н., Девришов Д.А., Фатахов К.Ф., Марзанов Н.С. Состояние исследований главного комплекса гистосовместимости (OLA) у овец // Аграрная наука. 2025. T. 390. N 1. C. 93–99. https://doi.org/10.32634/0869‐8155‐2025‐390‐01‐93‐99Marzanova S.N., Devrishova D.A., Fatakhov K.F., Marzanov N.S. Status of research on the major histocompatibility complex (OLA) in sheep. Agricultural science, 2025, vol. 390, no. 1, pp. 93–99. (In Russian) https://doi.org/ 10.32634/0869‐8155‐2025‐390‐01‐93‐99Herrmann‐Hoesing L.M., White S.N., Mousel M.R., Lewis G.S., Knowles D.P. Ovine progressive pneumonia provirus levels associate with breed and Ovar‐DRB1 // Immunogenetics. 2008. V. 60. N 12. P. 749–758. https://doi.org/10.1186/1297‐9686‐41‐17Herrmann‐Hoesing L.M., White S.N., Mousel M.R., Lewis G.S., Knowles D.P. Ovine progressive pneumonia provirus levels associate with breed and Ovar‐DRB1. Immunogenetics, 2008, vol. 60, no. 12, pp. 749–758. https://doi.org/10.1186/1297‐9686‐41‐17Gowane G.R., Sharma P., Kumar R., Misra S.S., Alex R., Vohra V., Chhotaray S., Dass G., Chopra A., Kandalkar Y., Vijay V., Choudhary A., Magotra A., Rajendran R. Cross‐population genetic analysis revealed genetic variation and selection in the Ovar‐DRB1 gene of Indian sheep breeds // Animal Biotechnology. 2023. V. 34. N 7. P. 2928–2939. https://doi.org/10.1080/10495398.2022.2125404Gowane G.R., Sharma P., Kumar R., Misra S.S., Alex R., Vohra V., Chhotaray S., Dass G., Chopra A., Kandalkar Y., Vijay V., Choudhary A., Magotra A., Rajendran R. Cross‐population genetic analysis revealed genetic variation and selection in the Ovar‐DRB1 gene of Indian sheep breeds. Animal Biotechnology, 2023, vol. 34, no.7, pp. 2928–2939. https://doi.org/10.1080/10495398.2022.2125404Gowane G.R., Sharma P., Kumar R., Misra S.S., Alex R., Vohra V., Chhotaray S, Sharma N., Chopra A., Kandalkar Y., Choudhary A., Magotra A. Population‐wide genetic analysis of OvarDQA1 and DQA2 loci across sheep breeds in India revealed their evolutionary importance and fitness of sheep in a tropical climate // Animal Biotechnology. 2023. V. 34. N 9. P. 4645–4657. https://doi.org/10.1080/10495398.2023.2180010Gowane G.R., Sharma P., Kumar R., Misra S. S., Alex R., Vohra V., Chhotaray S, Sharma N., Chopra A., Kandalkar Y., Choudhary A., Magotra A. Population‐wide genetic analysis of OvarDQA1 and DQA2 loci across sheep breeds in India revealed their evolutionary importance and fitness of sheep in a tropical climate. Animal Biotechnology, 2023, vol. 34, no. 9, pp. 4645–4657. https://doi.org/10.1080/10495398.2023.2180010Salim B., Nakao R., Chatanga E., Marcuzzi O., Ahmed Eissawi M., Almathen F., Hanotte O., Giovambattista G. Exploring genetic diversity and variation of Ovar‐DRB1 gene in Sudan Desert sheep using targeted next‐generation sequencing // BMC Genomics. 2024. V. 25. N 1. P. 2– 15. https://doi.org/10.1186/s12864‐024‐10053‐39Salim B., Nakao R., Chatanga E., Marcuzzi O., Ahmed Eissawi M., Almathen F., Hanotte O., Giovambattista G. Exploring genetic diversity and variation of Ovar‐DRB1 gene in Sudan Desert sheep using targeted next‐generation sequencing. BMC Genomics, 2024, vol. 25, no. 1, pp. 2–15. https://doi.org/10.1186/s12864‐024‐10053‐39Mahdy E.A., Mäkinen A., Chowdhary B.P., Andersson L., Gustavsson I. Chromosomal localization of the ovine major histocompatibility complex (OLA) by in situ hybridization // Hereditas. 1989. V. 111. N 1. P. 87–90. https://doi.org/10.1111/j.1601‐5223.1989.tb00381.xMahdy E.A., Mäkinen A., Chowdhary B.P., Andersson L., Gustavsson I. Chromosomal localization of the ovine major histocompatibility complex (OLA) by in situ hybridization. Hereditas, 1989, vol. 111, no. 1, pp. 87–90. https://doi.org/10.1111/j.1601‐5223.1989.tb00381.xBallingall K.T., Fardoe K., McKeever D.J. Genomic organisation and allelic diversity within coding and non‐coding regions of the Ovar‐DRB1 locus // Immunogenetics. 2008. V. 60. N 2. P. 95–103.Ballingall K.T., Fardoe K., McKeever D.J. Genomic organisation and allelic diversity within coding and non‐coding regions of the Ovar‐DRB1 locus. Immunogenetics, 2008, vol. 60, no. 2, pp. 95–103.Bay V., Keleş M., Aymaz R., Hatipoğlu E., Öner Y., Yaman Y. Documentation of extensive genetic diversity in the Ovar‐DRB1 gene in native Turkish sheep // Animal Biotechnology. 2021. V. 32. N 4. P. 507–518.Bay V., Keleş M., Aymaz R., Hatipoğlu E., Öner Y.,Yaman Y. Documentation of extensive genetic diversity in the Ovar‐DRB1 gene in native Turkish sheep. Animal Biotechnology, 2021, vol. 32, no. 4, pp. 507–518.Buzan E., Pokorny B., Urzi F., Duniš L., Bončina A., Iacolina L., Šprem N., Stipoljev S., Mereu P., Leoni G., Pirastru M., Safner T. Genetic variation of European mouflon depends on admixture of introduced individuals // Mammal Research. 2023. N 69. P. 145– 158. https://doi.org/10.1007/s13364‐023‐00726‐xBuzan E., Pokorny B., Urzi F., Duniš L., Bončina A., Iacolina L., Šprem N., Stipoljev S., Mereu P., Leoni G., Pirastru M., Safner T. Genetic variation of European mouflon depends on admixture of introduced individuals. Mammal Research, 2023, no. 69, pp. 145–158. https://doi.org/10.1007/s13364‐023‐00726‐xBallingall K.T., Tassi R. Sequence‐based genotyping of the sheep MHC class II DRB1 locus // Immunogenetics. 2010. V. 62. N 1. P. 31–39.Ballingall K.T., Tassi R. Sequence‐based genotyping of the sheep MHC class II DRB1 locus. Immunogenetics, 2010, vol. 62, no. 1, pp. 31–39.Polat M., Aida Y., Takeshima S.N., Aniwashi J., Halik M. The diversity of major histocompatibility complex class II DRB1 gene in sheep breeds from Xinjiang, China // Tissue Antigens. 2015. V. 85. N 1. P. 50–57. https://doi.org/10.1111/tan.12480Polat M., Aida Y., Takeshima S.N., Aniwashi J., Halik M. The diversity of major histocompatibility complex class II DRB1 gene in sheep breeds from Xinjiang, China. Tissue Antigens, 2015, vol. 85. no. 1, pp. 50–57. https://doi.org/10.1111/tan.12480Yaman Y., Bay V., Aymaz R., Keleş M., Öner Y., Teferedegn E.Y., Ün C. A novel 2 bp deletion variant in Ovine‐DRB1 gene is associated with increased Visna/maedi susceptibility in Turkish sheep // Scientific Reports. 2021. V. 11. Article id: 14435. p. 1–11. https://doi.org/10.1038/s41598‐021‐93864‐8Yaman Y., Bay V., Aymaz R., Keleş M., Öner Y., Teferedegn E.Y., Ün C. A novel 2 bp deletion variant in Ovine‐DRB1 gene is associated with increased Visna/maedi susceptibility in Turkish sheep. Scientific Reports, 2021, vol. 11, article id: 14435, pp. 1–11. https://doi.org/10.1038/s41598‐021‐93864‐8Huang W., Dicks K.L., Hadfield J.D., Johnston S.E., Ballingall K.T., Pemberton J.M. Contemporary selection on MHC genes in a freeliving ruminant population // Ecology Letters. 2022. V. 25. N 4. P. 828–838. https://doi.org/10.1111/ele.13957Huang W., Dicks K.L., Hadfield J.D., Johnston S.E., Ballingall K.T., Pemberton J.M. Contemporary selection on MHC genes in a freeliving ruminant population. Ecology Letters, 2022, vol. 25, no. 4, pp. 828–838. https://doi.org/10.1111/ele.13957Stear M., Preston S., Piedrafita D., Donskow‐Łysoniewska K. The Immune Response to Nematode Infection // International Journal of Molecular Sciences. 2023. V. 24. Article id: 2283. pp. 1–18. https://doi.org/10.3390/ijms24032283Stear M., Preston S., Piedrafita D., Donskow‐Łysoniewska K. The Immune Response to Nematode Infection. International Journal of Molecular Sciences, 2023, vol. 24, article id: 2283, pp. 1–18. https://doi.org/10.3390/ijms24032283Омарова Ф.А., Дроков М.Ю., Хамаганова Е.Г. Главный комплекс гистосовместимости: история открытия, эволюция, строение, значение при трансплантации аллогенных гемопоэтических стволовых клеток // Трансплантология. 2023. T. 15. N 2. C. 251–265. https://doi.org/10.23873/2074‐0506‐2023‐15‐2‐251‐265Omarova F.A., Drokov M.Yu., Khamaganova E.G. Major histocompatibility complex: history of discovery, evolution, structure, significance for transplantation of allogenetic hematopoietic stem cells. Transplantologiya. The Russian Journal of Transplantation, 2023, vol. 15, no. 2, pp. 251–265. (In Russian) https://doi.org/10.23873/2074‐0506‐2023‐15‐2‐251‐265Shen H., Han G., Jia B., Jiang S., Du Y. MHC‐DRB1/DQB1 Gene Polymorphism and Its Association with Resistance/Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep // Journal Parasitology Research. 2014. Article id: 272601. P. 1–7. https://dx.doi.org/10.1155/2014/272601Shen H., Han G., Jia B., Jiang S., Du Y. MHC‐DRB1/DQB1 Gene Polymorphism and Its Association with Resistance/Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep. Journal Parasitology Research, 2014, article id: 272601, pp. 1–7. https://dx.doi.org/10.1155/2014/272601Esmailnejad A., Ganjiani V., Hosseini‐Nasab E., Nazifi S. Association of Ovar‐DRB1 alleles with innate immune responses in sheep // Vetrinary Medicine and Science. 2022. V. 8. N 2. P. 752–757. https://doi.org/10.1002/vms3.683Esmailnejad A., Ganjiani V., Hosseini‐Nasab E., Nazifi S. Association of Ovar‐DRB1 alleles with innate immune responses in sheep. Vetrinary Medicine and Science, 2022, vol. 8, no. 2, pp. 752–757. https://doi.org/10.1002/vms3.683Марзанова С.Н., Девришов Д.А., Жучков В.А., Николаева Е.А., Марзанов Н.С. Сравнение аллелей гена DRB1 двух популяций овец романовской породы методами рестрикционного картирования и секвенирования // Биотехнология. 2025. Т. 41. N 1. С. 21–33. https://doi.org/10.56304/S0234275825010090Marzanova S.N., Devrishova D.A., Zuchkova V.A., Nikolaeva E.A., Marzanov N.S. Comparison of DRB1 Gene Alleles in Two Populations of Romanov Sheep Breed by Restriction Mapping and Sequencing. Biotechnology, 2025, vol. 41, no. 1, pp. 21–33. (In Russian) DOI: 10.56304/S0234275825010090Maccari G., Robinson J., Barker D.J., Yates A.D., Hammond J.A., Marsh S.G.E. The 2024 IPD‐MHC database update: a comprehensive resource for major histocompatibility complex studies // Nucleic Acids Research. 2025. V. 53. N D1. P. D457–D461. https://doi.org/10.1093/nar/gkae932.24Maccari G., Robinson J., Barker D.J., Yates A.D., Hammond J.A., Marsh S.G.E. The 2024 IPD‐MHC database update: a comprehensive resource for major histocompatibility complex studies. Nucleic Acids Research, 2025, vol. 53, no. D1, pp. D457–D461. https://doi.org/10.1093/nar/gkae932Peakall R., Smouse P.E. GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research ‐ an update // Bioinformatics. 2012. V. 28. N 19. P. 2537–2539. https://doi.org/10.1093/bioinformatics/bts460Peakall R., Smouse P.E. GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research‐‐an update. Bioinformatics, 2012, vol. 28, no. 19, pp. 2537–2539. https://doi.org/10.1093/bioinformatics/bts460Cinar M.U., Mousel M.R., Herrmann‐Hoesing L.M., Taylor J.B., White S.N. Ovar‐DRB1 haplotypes *2001 and *0301 are associated with sheep growth and ewe lifetime prolificacy // Gene. 2016. V. 595. N 2. P. 187–192. https://doi.org/10.1016/j.gene.2016.10.004Cinar M.U., Mousel M.R., Herrmann‐Hoesing L.M., Taylor J.B., White S.N. Ovar‐DRB1 haplotypes *2001 and *0301 are associated with sheep growth and ewe lifetime prolificacy. Gene, 2016, vol. 595, no. 2, pp. 187–192. https://doi.org/10.1016/j.gene.2016.10.004Hassan M., Good B., Hanrahan J.P., Campion D., Sayers G., Mulcahy G., Sweeney T. The dynamic influence of the DRB1*1101 allele on the resistance of sheep to experimental Teladorsagia circumcincta infection // Veterinary Research. 2011. V. 42. N 46. P. 1–10. https://doi.org/10.1186/1297‐9716‐42‐46Hassan M., Good B., Hanrahan J. P., Campion D., Sayers G., Mulcahy G., Sweeney T. Sweeney. The dynamic influence of the DRB1*1101 allele on the resistance of sheep to experimental Teladorsagia circumcincta infection. Veterinary Research, 2011, vol.42,

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