Alleles and haplotypes of bone marrow donors recruited in the Оrenburg region
https://doi.org/10.18699/SSMJ20250307
Abstract
Aim of the study was to investigate the frequency of occurrence of HLA alleles and five-locus haplotypes in hematopoietic stem cell donors - residents of the Orenburg region.
Material and methods. HLA typing of 5529 potential donors of the Orenburg region of the Russian Federation using NGS technology in 2-field resolution at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci was performed.
Results and discussion. 74 alleles were identified at the HLA-A locus, 108 at the HLA-B locus, 68 at the HLA-C locus, 65 at the HLA-DRB1 locus, and 37 at the HLA-DQB1 locus. The most common alleles are HLA-A*02:01 (25.85 %), HLA-A*03:01 (12.96 %), HLA-A*01:01 (11.66 %), HLA-B*07:02 (10.70 %), HLA-B*18:01 (7.40 %), HLA-B*08:01 (6.39 %), HLA-C*04:01 (13.22 %), HLA-C*07:02 (12.43 %), HLA-C*07:01 (11.70 %), HLA-DRB1*07:01 (13.75 %), HLA-DRB1*15:01 (10.93 %), HLA-DRB1*01:01 (10.55 %), HLA-DQB1*03:01 (21.23 %), HLA-DQB1*05:01 (13.23 %), HLA-DQB1*02:02 (11.02 %). Among five-locus haplotype in the studied population the most common is HLA-A*01:01~HLA-C*07:01~HLA-B*08:01~HLA-DRB1*03:01~HLA-DQB1*02:01 (3.66 %). 26 new alleles have been described.
Conclusions. The examined population of donors recruited in the Orenburg region, according to the distribution of the most common alleles and haplotypes, has great similarity with the studied populations of the European part of Russia, however, a large number of identified rare and new alleles indicates the relevance of further research and recruitment of donors in this region in order to increase the genetic diversity of the Federal Register, which will increase the likelihood of matching a donor for any patient in need of hematopoietic stem cell transplantation.
About the Authors
D. N. SmirnovaRussian Federation
Darya N. Smirnova, candidate of biological sciences
610027; Krasnoarmeyskaya st., 72; Kirov
M. A. Loginova
Russian Federation
Maria A. Loginova, doctor of biological sciences
610027; Krasnoarmeyskaya st., 72; 610000; Moskovskaya st., 36; Kirov
O. A. Makhova
Russian Federation
Olga A. Makhova
610027; Krasnoarmeyskaya st., 72; Kirov
I. P. Obukhov
Russian Federation
Ivan P. Obukhov
610027; Krasnoarmeyskaya st., 72; Kirov
J. I. Dudina
Russian Federation
Julia I. Dudina
610027; Krasnoarmeyskaya st., 72; Kirov
N. A. Morozova
Russian Federation
Nadezhda A. Morozova
610027; Krasnoarmeyskaya st., 72; Kirov
I. V. Paramonov
Russian Federation
Igor V. Paramonov, doctor of medical sciences
610027; Krasnoarmeyskaya st., 72; Kirov
References
1. Barcer D.J., Maccari G., Georgiou X., Cooper M.A, Flicek P., Robinson J., Marsh S.G.E. The IPD-IMGT/HLA Database. Nucleic Acids Res. 2023;51(D1):1053–1060. doi: 10.1093/nar/gkac1011
2. Jöris M.M., Lankester A.C., Borne P.V., Kuball J., Bierings M., Cornelissen J.J., Groenendijk-Sijnke M.E., Holt B., Haasnoot G.W., Zanden H.G., … Oudshoorn M. The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT. Bone Marrow Transplantat. 2013;48(4):483–490. doi: 10.1038/bmt.2012.189
3. Petersdorf E.W., Malkki M., Gooley T.A., Martin P.J., Guo Z. MHC haplotype matching for unrelated hematopoietic cell transplantation. PLoS Med. 2007;4(1):e8. doi: 10.1371/journal.pmed.0040008
4. Sacchi N., Castagnetta M., Miotti V., Garbarino L., Gallina A. High-resolution analysis of the HLA-A, -B, -C and -DRB1 alleles and national and regional haplotype frequencies based on 120 926 volunteers from the Italian Bone Marrow Donor Registry. HLA. 2019;94(3):285–295. doi: 10.1111/tan.13613
5. Schmidt A.H., Solloch U.V., Pingel J., Sauter J., Böhme I., Cereb N., Dubicka K., Schumacher S., Wachowiak J., Ehninger G. Regional HLA differences in Poland and their effect on stem cell donor registry planning. PLOS One. 2013;9(9):1–10. doi: 10.1371/journal.pone.0073835
6. Petersdorf E.W., Malkki M., Horowitz M.M., Spellman S.R., Haagenson M.D., Wang T. Mapping MHC haplotype effects in unrelated donor hematopoietic cell transplantation. Blood. 2013;121(10):1896–1905. doi: 10.1182/blood-2012-11-465161
7. Gonzalez-Galarza F.F., Takeshita L.Y., Santos E.J., Kempson F., Maia M.H., da Silva A.L., Teles e Silva A.L., Ghattaoraya G.S., Alfirevic A., Jones A.R, Middleton D. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Research. 2015;43:784–788. doi: 10.1093/nar/gku1166
8. The Allele Frequency Net Database. Available at: http://www.allelefrequencies.net/
9. Makarenko O.A., Alyansky A.L., Ivanova N.E., Kucher M.A., Babenko E.V., Estrina M.A., Pevtsov D.E., Golovacheva A.A., Kuzmich E.V., Afanasyev B.V. Effectiveness of search for an unrelated donor of hematopoietic stem cells using Russian date base “Bone marrow donor search”: experience of Raisa Gorbacheva Memorial Institute for Children Oncology, Hematology and Transplantation. Klinicheskaya onkogematologiya = Clinical Oncohematology. 2017;10(1):39–44. [In Russian]. doi: 10.21320/2500-2139-2017-10-1-39-44
10. Loginova M.A., Malysheva N.A., Minaeva N.V., Paramonov I.V. Evaluation of the efficiency of the activity of the register of potential donors of hematopoietic stem cells. Gematologiya i transfuziologiya = Hematology and Transfusiology. 2020;65(3):291–298. [In Russian]. doi: 10.35754/0234-5730-2020-65-3-291-298
11. Bubnova L.N., Kuzmich E.V., Pavlova I.E., Belyaeva E.V., Terentyeva M.A. Comparative analysis of immunogenetic characteristics of potential hematopoietic stem cell donors from registries of two Russian megacities. Meditsinskaya immunologiya = Medical Immunology. 2022;24(5):1047–1056. [In Russian]. doi: 10.15789/1563-0625-CAO-2539
12. Bubnova L.N., Pavlova I.E., Berkos A.S., Moiseeva L.M., Erokhina L.V., Bakai V.V., Belyaeva E.V., Glazanova T.V., Rozanova O.E., Chubukina Zh.V., Ryzhevnina Yu.E., Chechetkin A.V. Immunogenetic characteristics of hematopoietic stem cell donors from the Northwestern region of Russia. Vestnik gematologii = Bulletin of Hematology. 2016;11(2):11–12. [In Russian].
13. Trusova L.M., Klyuchnikov D.Yu., Vavilov M.N., Suslova T.A., Tyumina O.V. The frequency of occurrence of HLA alleles and haplotypes in the Russian population of the Samara and Chelyabinsk regions. Vestnik gematologii = Bulletin of Hematology. 2018;14(2):47. [In Russian].
14. Dudina Yu.I., Loginova M.A., Smirnova D.N., Obukhov I.P., Makhova O.A., Morozova N.A., Paramonov I.V. Assessment of immunogenetic characteristics of donors located in the Kirov region. Сurrent issues in transfusiology and oncohematology : proc. conf., Kirov, November 7–8, 2024. Kirov: O-Kratkoe, 2024. P. 5–18. [In Russian].
15. Loginova M.A., Smirnova D.N., Kutyavina S.S., Makhova O.A., Paramonov I.V., Tataeva Z.M., Tankaeva Kh.S., Kabardieva A.I. Distribution of HLA alleles and haplotypes in the population of the North Caucasus Transfuziologiya = Transfusiology. 2020;21(1):57–67. [In Russian].
16. Abdrakhimova A.R., Leonov E.A., Khamaganova E.G. HLA genes and haplotypes in вashkirs-donors of hematopoietic stem cells from the registry of the Federal State Budgetary Institution “National Medical Research Center of Hematology” of the Ministry of Health of Russia, typed by NGS. Vestnik gematologii = Bulletin of Hematology. 2019;15(4):28. [In Russian].
17. Orenburg region. Available at: clck.ru/3M768z [In Russian].
18. Chibilev A.A. Nature of the Orenburg region (Part I. Physical-geographical and historical-geographical essay). Orenburg, 1995. 76 p. [In Russian].
19. National composition of the population of the Orenburg region according to the results of the 2020 All-Russian Population Census Available at: clck.ru/3M76CF [In Russian].
20. Robinson J., Barker D.J., Georgiou X., Cooper M.A., Flicer P., Marsh S.G.E. IPD-IMGT/HLA Database. Nucleic Acids Research. 2020;48(D1):948–955. doi: 10.1093/nar/gkz950
21. Marsh S.G.E, Albert E.D., Bodmer W.F., Bontrop R.E., Dupont B., Erlich H.A, Fernández-Viña M., Geraghty D.E., Holdsworth R., Hurley C.K., … Trowsdale J. Nomenclature for factors of the HLA system. Tissue Antigens. 2010;75(4):291–455. doi: 10.1111/j.1399-0039.2010.01466.x
22. Sanchez-Mazas A., Nunes J.M., Middleton D., Sauter J., Buhler S., McCabe A., Hofmann J., Baier D.M., Schmidt A.H., Nicoloso G., … Fleischhauer K. Common and Well-documented HLA alleles over all of Europe and within European sub-regions: a catalogue from European Federation of Immunogenetics. HLA. 2017;89(2):104–113. doi: 10.1111/tan.12956
23. Allele Frequency Net Database. Available at: http://www.allelefrequencies.net
24. Evseeva I., Spurkland A., Thorsby E., Smerdel A., Tranebjaerg L., Boldyreva M., Groudakova E., Gouskova I., Alexeev L.L. HLA profile of three ethnic groups living in the North-Western region of Russia. Tissue Antigens. 2002;59(1):38–43. doi: 10.1034/j.1399-0039.2002.590107.x
25. Arnaiz-Villena A., Martinez-Laso J., Moscoso J., Livshits G., Zamora J., Gomez-Casado E., Silvera-Redondo C., Melvin K., Crawford M.H. HLA alleles of Chuvash from European Russia: admixture of Central European and Mediterranean populations. Human. Biology. 2003;75(3):375–392. doi: 10.1353/hub.2003.0040
26. Martinez-Laso J., Sartakova M., Allende L., Konenkov V., Moscoso J., Silvera-Redondo C., Pacho A., Trapaga J., Gomez-Casado E., Arnaiz-Villena A. HLA molecular markers in Tuvinians: a population with both Oriental and Caucasoid characteristics. Ann. Hum. Genet. 2001;65(Pt 3):245–261. doi: 10.1017/S0003480001008624
27. Smirnova D., Loginova M., Druzhinina S., Paramonov I., Abramova A., Simakova T. Distributions of HLA-A, -B, -C, -DRB1 and -DQB1 alleles typed by next generation sequencing in russian volunteer donors. HLA. 2023;101(6):623–633. doi: 10.1111/tan.15007
28. Cano P., Klitz W., Mask S.J., Maiers M., Marsh S.G., Noreen H., Reed E.F., Senitzer D., Setterholm M., Smith A., Fernández-Viña M. Common and well-documented HLA alleles: report of the Ad-Hoc commit-tee of the american society for histocompatibility and immunogenetics. Hum. Immunol. 2007;68(5):392–417. doi: 10.1016/j.humimm.2007.01.014
29. He Y., Li J., Mao W., Zhang D., Liu M., Shan X., Zhang B., Zhu C., Shen J., Deng Z, … Du D. HLA common and well-documented alleles in China. HLA 2018;92 (4):199–205. doi: 10.1111/tan.13358
30. Hurley C.K., Kempenich J., Wadsworth K., Sauter J., Hofmann J.A., Schefzyk D., Schmidt A.H., Galarza P., Cardozo M.B.R., Dudkiewicz M., … Dehn J. Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0. HLA. 2020;95(6):516–531. doi: 10.1111/tan.13811
31. Mack S.J., Cano P., Hollenbach J.A., He J., Hurley C.K., Middleton D., Moraes M.E., Pereira S.E., Kempenich J.H., Reed E.F., … Fernandez-Vina M. Common and well-documented HLA alleles: 2012 update to the CWD catalogue. Tissue Antigens. 2013;81(4):194–203. doi: 10.1111/tan.12093