Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences69381510.31857/S0016675825080071ГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleAnalysis of the Spectrum of the mtDNA Haplogroups in Patients with Hearing Loss Carrying the Likely Pathogenic Ultra-Rare m.1494C>T Variant in the MT-RNR1 GeneАНАЛИЗ СПЕКТРА ГАПЛОГРУПП мтДНК У ПАЦИЕНТОВ С НАРУШЕНИЯМИ СЛУХА, НЕСУЩИХ ВЕРОЯТНО-ПАТОГЕННЫЙ УЛЬТРАРЕДКИЙ ВАРИАНТ m.1494C>T В ГЕНЕ MT-RNR1BorisovaT. V.БорисоваТ. В.barashkov2004@mail.ruCherdonovaA. M.ЧердоноваА. М.barashkov2004@mail.ruPshennikovaV. G.ПшенниковаВ. Г.barashkov2004@mail.ruTeryutinF. M.ТерютинФ. М.barashkov2004@mail.ruMorozovI. V.МорозовИ. В.barashkov2004@mail.ruBondarA. A.БондарьА. А.barashkov2004@mail.ruBaturinaO. A.БатуринаО. А.barashkov2004@mail.ruKabilovM. R.КабиловМ. Р.barashkov2004@mail.ruRomanovG. P.РомановГ. П.barashkov2004@mail.ruSolovyevA. V.СоловьевА. В.barashkov2004@mail.ruFedorovaS. A.ФедороваС. А.barashkov2004@mail.ruBarashkovN. A.БарашковН. А.barashkov2004@mail.ruInstitute of Natural Sciences, M.K. Ammosov North-Eastern Federal UniversityИнститут естественных наук Северо-Восточного федерального университета им. М.К. АммосоваYakut Scientific Center of Complex Medical ProblemsЯкутский научный центр комплексных медицинских проблемInstitute of Natural Sciences, M.K. Ammosov North-Eastern Federal UniversityYakut Scientific Center of Complex Medical ProblemsИнститут естественных наук Северо-Восточного федерального университета им. М.К. АммосоваЯкутский научный центр комплексных медицинских проблемNovosibirsk State UniversityInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of SciencesНовосибирский государственный университетИнститут химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of SciencesИнститут химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукInstitute of Natural Sciences, M.K. Ammosov North-Eastern Federal UniversityИнститут естественных наук Северо-Восточного федерального университета им. М.К. АммосоваInstitute of Natural Sciences, M.K. Ammosov North-Eastern Federal UniversityYakut Scientific Center of Complex Medical ProblemsИнститут естественных наук Северо-Восточного федерального университета им. М.К. АммосоваЯкутский научный центр комплексных медицинских проблемInstitute of Natural Sciences, M.K. Ammosov North-Eastern Federal UniversityЯкутский научный центр комплексных медицинских проблем15082025618VOL 61, NO8 (2025)ТОМ 61, №8 (2025)708619102025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/693815

The contribution of the m.1494C>T variant of the MT-RNR1 gene associated with aminoglycoside-induced deafness (MT-RNR1, OMIM 561000) to the etiology of hearing loss (HL)is still poorly studied. In this regard, aim of the study – screening of the m.1494C>T gene MT-RNR1 among patients with HL in the Republic of Buryatia located in the Baikal Lake region of Russia and reconstructed the mitochondrial lineages in 27 patients with m.1494C>T variant from different regions of the world. From available data and based on the results of a genome-wide analysis of mtDNA of one patient with m.1494C>T detected in this study we are reconstructed the mitochondrial lineages in 27 patients with m.1494C>T variant from different regions of the world. As a result, 19 different mtDNA haplogroups were identified, which likely indicates the independent origin of the m.1494C>T variant on the different mitochondrial background. However, in patients with m.1494C>T were found the high frequency of haplogroup A* (18.5%, 5/27), which in 13 times exceeded (χ2 = 45.274; p < 0.001) the mean frequency of this haplogroup (1.45%, 519/35748) in worldwide population. The over representation of haplogroup A* among patients with m.1494C>T may be due of their common ancestry. The possible influence of a founder effect on the prevalence of the MT-RNR1, the target screening of the m.1494C>T variant in previously unexplored cohorts of patients with HL is a more relevant, primarily in regions where the haplogroups A* and A2 were found – in Asia and America.

Вклад в этиологию потери слуха ультраредкого варианта m.1494C>T гена MT-RNR1 мтДНК, ассоциированного с аминогликозид-индуцированной глухотой (MT-RNR1, OMIM 561000), остается неизученным в большинстве выборок индивидов с нарушениями слуха. В связи с этим цель настоящей работы – скрининг m.1494C>T гена MT-RNR1 мтДНК среди пациентов с нарушениями слуха в Республике Бурятия, с последующим анализом выявленных в мире митохондриальных линий, несущих данный ультраредкий вариант. Из открытых баз данных, литературных источников, а также по результатам полногеномного анализа мтДНК одного пациента с m.1494C>T, обнаруженного в настоящей работе, нами был проведен анализ митохондриальных линий для 27 пациентов из разных регионов мира, у которых был обнаружен данный ультраредкий вариант. У пациентов с m.1494C>T идентифицировано 19 различных гаплогрупп мтДНК, что, вероятно, свидетельствует о независимом возникновении варианта m.1494C>T. Однако в спектре выявленных гаплогрупп мы обнаружили преобладание гаплогруппы А*, частота которой в 13 раз превышала (χ2 = 45.274, p < 0.001) среднее значение частоты данной гаплогруппы в изученных ранее популяциях мира (1.45%, 519/35748). Избыточность гаплогруппы А* у индивидов с m.1494C>T может являться следствием их общего происхождения. Вероятность влияния эффекта основателя на распространенность MT-RNR1 повышает релевантность целенаправленного поиска m.1494C>T в ранее неисследованных когортах пациентов с нарушениями слуха, в первую очередь в регионах, где встречается гаплогруппа А* и ее дочерняя линия А2, – в Азии и в Америке.

m.1494C>TMT-RNR1 geneaminoglycoside-induceddeafnessmtDNAhaplogroup A*Baikal Lake regionm.1494C>Tген MT-RNR1аминогликозид-индуцированная потеря слухамтДНКгаплогруппа А*регион озБайкалMorton C.C., Nance W.E. Newborn hearing scree- ning – a silent revolution // N. Engl. J. Med. 2006. V. 354. № 20. P. 2151–2164. https://doi.org/10.1056/NEJMra050700Del Castillo F.J., Del Castillo I. DFNB1 non-syndromic hearing impairment: Diversity of mutations and associated phenotypes // Front. Mol. Neurosci. 2017. V. 10. P. 428. https://doi.org/10.3389/fnmol.2017.00428Del Castillo I., Morín M., Domínguez-Ruiz M., Moreno-Pelayo M.A. Genetic etiology of non-syndromic hearing loss in Europe // Hum. Genet. 2022. V. 141. P. 683–696. https://doi.org/10.1007/s00439-021-02425-6Jin L., Yang A., Zhu Y. et al. Mitochondrial tRNA(Ser(UCN)) gene is the hot spot for mutations associated with aminoglycoside-induced and non-syndromic hearing loss // Biochem. Biophys. Res. Commun. 2007. V. 361. № 1. P. 133–139. https://doi.org/10.1016/j.bbrc.2007.06.171Richard E.M., Santos-Cortez R.L.P., Faridi R. et al. Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss // Hum. Mutat. 2019. V. 40. № 1. P. 53–72. https://doi.org/10.1002/humu.23666Sloan-Heggen C.M., Bierer A.O., Shearer A.E. et al. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss // Hum. Genet. 2016. V. 135. № 4. P. 441. https://doi.org/10.1007/s00439-016-1648-8Zazo Seco C., Wesdorp M., Feenstra I. et al. The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in the Netherlands // Eur. J. Hum. Genet. 2017. V. 25. № 3. P. 308. https://doi.org/10.1038/ejhg.2016.182Baux D., Vaché C., Blanchet C. et al. Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients // Sci. Rep. 2017. V. 7. № 1. P. 16783. https://doi.org/10.1038/s41598-017-16846-9Boudewyns A., van den Ende J., Sommen M. et al. Role of targeted next generation sequencing in the etiological work-up of congenitally deaf children // Otol. Neurotol. 2018. V. 39. № 6. P. 732. https://doi.org/10.1097/MAO.0000000000001847Wu C.C., Tsai C.Y., Lin Y.H. et al. Genetic epidemiology and clinical features of hereditary hearing impairment in the Taiwanese population // Genes. 2019. V. 10. № 10. P. 772. https://doi.org/10.3390/genes10100772García-García G., Berzal-Serrano A., García-Díaz P. et al. Improving the management of patients with hearing loss by the implementation of an NGS panel in clinical practice // Genes (Basel). 2020. V. 11. № 12. P. 1467. https://doi.org/10.3390/genes11121467Doll J., Vona B., Schnapp L. et al. Genetic spectrum of syndromic and non-syndromic hearing loss in Pakistani families // Genes (Basel). 2020. V. 11. № 11. P. 1329. https://doi.org/10.3390/genes11111329Usami S.I., Nishio S.Y. The genetic etiology of hearing loss in Japan revealed by the social health insurance-based genetic testing of 10K patients // Hum. Genet. 2022. V. 141. № 3–4. P. 665. https://doi.org/10.1007/s00439-021-02371-3Downie L., Halliday J., Burt R. et al. Exome sequen-cing in infants with congenital hearing impairment: A population-based cohort study // Eur. J. Hum. Genet. 2020. V. 28. № 5. P. 587. https://doi.org/10.1038/s41431-019-0553-8Tropitzsch A., Schade-Mann T., Gamerdinger P. et al. Diagnostic yield of targeted hearing loss gene panel sequencing in a large German cohort with a balanced age distribution from a single diagnostic center: An eight-year study // Ear Hear. 2022. V. 43. № 3. P. 1049. https://doi.org/10.1097/AUD.0000000000001159Seligman K.L., Shearer A.E., Frees K. et al. Genetic causes of hearing loss in a large cohort of cochlear implant recipients // Otolaryngol. Head Neck Surg. 2022. V. 166. № 4. P. 734. https://doi.org/10.1177/01945998211021308Pan J., Ma S., Teng Y. et al. Wu. Whole-exome sequencing identifies genetic variants of hearing loss in 113 Chinese families // Clin. Chim. Acta. 2022. V. 532. P. 53–60. https://doi.org/10.1016/j.cca.2022.05.020Luo H., Yang Y., Wang X. et al. Concurrent newborn hearing and genetic screening of common hearing loss variants with bloodspot-based targeted next generation sequencing in Jiangxi province // Front. Pediatr. 2022. V. 10. https://doi.org/10.3389/fped.2022.1020519.Zeng B., Xu H., Yu Y. et al. Increased diagnostic yield in a cohort of hearing loss families using a comprehensive stepwise strategy of molecular tes- ting // Front. Genet. 2022. V. 13. https://doi.org/10.3389/fgene.2022.1057293Elsayed O., Al-Shamsi A. Mutation spectrum of non-syndromic hearing loss in the UAE, a retrospective cohort study and literature review // Mol. Genet. Genomic Med. 2022. V. 10. № 11. P. e2052. https://doi.org/10.1002/mgg3.2052Pál M., Nagy D., Neller A. et al. Genetic etiology of nonsyndromic hearing loss in Hungarian patients // Int. J. Mol. Sci. 2023. V. 24. № 8. P. 7401. https://doi.org/10.3390/ijms24087401Ma J., Ma X., Lin K. et al. Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel // Hum. Genomics. 2023. V. 17. № 1. P. 1. https://doi.org/10.1186/s40246-022-00449-1Fallerini C., Picchiotti N., Baldassarri M. et al. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity // Hum. Genet. 2022. V. 141. № 1. P. 147–173. https://doi.org/10.1007/s00439-021-02397-7Kong Q.P., Yao Y.G., Sun C. et al. Phylogeny of East Asian mitochondrial DNA lineages inferred from complete sequences // Am. J. Hum. Genet. 2003. V. 73. № 3. P. 671–676. https://doi.org/10.1086/377718.Zhao H., Li R., Wang Q. et al. Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese fa- mily // Am. J. Hum. Genet. 2004. V. 74. № 1. P. 139–152. https://doi.org/10.1086/381133Hutchin T., Haworth I., Higashi K. et al. A molecular basis for human hypersensitivity to aminoglycoside antibiotics // Nucl. Acids Res. 1993. V. 21. № 18. P. 4174–4179. https://doi.org/10.1093/nar/21.18.4174Guan M.X., Fischel-Ghodsian N., Attardi G. Bio-chemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation // Hum. Mol. Genet. 1996. V. 5. № 7. P. 963–971. https://doi.org/10.1093/hmg/5.7.963Hamasaki K., Rando R.R. Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness // Biochemistry. 1997. V. 36. № 40. P. 12323–12328. https://doi.org/10.1021/bi970962rEstivill X., Govea N., Barceló E. et al. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides // Am J. Hum. Genet. 1998. V. 62. № 1. P. 27–35. https://doi.org/10.1086/301676Hobbie S.N., Bruell C.M., Akshay S. et al. Mito-chondrial deafness alleles confer misreading of the genetic code // Proc. Natl Acad. Sci. USA. 2008. V. 105. № 9. P. 3244–3249. https://doi.org/10.1073/pnas.0707265105Greber B.J., Bieri P., Leibundgut M. et al. Ribosome. The complete structure of the 55S mammalian mitochondrial ribosome // Science. 2015. V. 348. № 6232. P. 303–308. https://doi.org/10.1126/science.aaa3872Rovcanin B., Jancic J., Samardzic J. et al. In silico model of mtDNA mutations effect on secondary and 3D structure of mitochondrial rRNA and tRNA in Leber’s hereditary optic neuropathy // Exp. Eye Res. 2020. V. 201. https://doi.org/10.1016/j.exer.2020.108277Rodríguez-Ballesteros M., Olarte M., Aguirre L.A. et al. Molecular and clinical characterization of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C>T mutation in the mitochondrial 12S rRNA gene // J. Med. Genet. 2006. V. 43. № 11. P. e54. https://doi.org/10.1136/jmg.2006.042440Johnson R.F., Cohen A.P., Guo Y. et al. Genetic mutations and aminoglycoside-induced ototoxicity in neonates // Otolaryngol. Head Neck Surg. 2010. V. 142. № 5. P. 704–707. https://doi.org/10.1016/j.otohns.2010.01.030Zhu Y., Li Q., Chen Z. et al. Mitochondrial haplotype and phenotype of 13 Chinese families may suggest multi-original evolution of mitochondrial C1494T muta- tion // Mitochondrion. 2009. V. 9. № 6. P. 418–428. https://doi.org/10.1016/j.mito.2009.07.006Barbarino J.M., McGregor T.L., Altman R.B., Klein T.E. PharmGKB summary: very important pharmacogene information for MT-RNR1 // Pharmacogenet. Genomics. 2016. V. 26. № 12. P. 558–567. https://doi.org/10.1097/FPC.0000000000000247Kalapala S.K., Hobbie S.N., Böttger E.C., Shcherba-kov D. Mutation K42R in ribosomal protein S12 does not affect susceptibility of Mycobacterium smegmatis 16S rRNA A-site mutants to 2-deoxystreptamines // PLoS One. 2010. V. 5. № 8. P. e11960. https://doi.org/10.1371/journal.pone.0011960Wang Q., Li Q.Z., Han D. et al. Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation // Biochem. Biophys. Res. Commun. 2006. V. 340. № 2. P. 583–588. https://doi.org/10.1016/j.bbrc.2005.12.045Han D., Dai P., Zhu Q. et al. The mitochondrial tRNA(Ala) T5628C variant may have a modifying role in the phenotypic manifestation of the 12S rRNA C1494T mutation in a large Chinese family with hearing loss // Biochem. Biophys. Res. Commun. 2007. V. 357. № 2. P. 554–560. https://doi.org/10.1016/j.bbrc.2007.03.199Yuan H., Chen J., Liu X. et al. Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss // Biochem. Biophys. Res. Commun. 2007. V. 362. № 1. P. 94–100. https://doi.org/10.1016/j.bbrc.2007.07.161Chen B., Sun D., Yang L. et al. Mitochondrial ND5 T12338C, tRNA(Cys) T5802C, and tRNA(Thr) G15927A variants may have a modifying role in the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in three Han Chinese pedigrees // Am. J. Med. Genet. A. 2008. V. 146A. № 10. P. 1248–1258. https://doi.org/10.1002/ajmg.a.32285Van Oven M., Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation // Hum. Mutat. 2009. V. 30. № 2. P. E386–E394. https://doi.org/10.1002/humu.20921Okonechnikov K., Golosova O., Fursov M. UGENE team. unipro UGENE: A unified bioinformatics tool-kit // Bioinformatics. 2012. V. 28(8). P. 1166–1167. https://doi.org/10.1093/bioinformatics/bts091Tamura K., Stecher G., Kumar S. MEGA11: Molecular evolutionary genetics analysis version 11 // Mol. Biol. Evol. 2021. V. 38(7). P. 3022–3027. https://doi.org/10.1093/molbev/msab120Andrews R., Kubacka I., Chinnery P. et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA // Nat. Genet. 1999. V. 23. № 2. P. 147. https://doi.org/10.1038/13779. PMID: 10508508Pshennikova V., Teryutin F., Cherdonova A. et al. The GJB2 (Cx26) gene variants in patients with hearing impairment in the Baikal lake region (Russia) // Genes. 2023. V. 14. № 5. P. 1001. https://doi.org/10.3390/genes14051001Borisova T., Cherdonova A., Pshennikova V. et al. High prevalence of m.1555A > G in patients with hearing loss in the Baikal lake region of Russia as a result of founder effect // Sci. Rep. 2024. V. 14. № 1. P. 15342. https://doi.org/10.1038/s41598-024-66254-zWeissensteiner H., Pacher D., Kloss-Brandstät- ter A. et al. HaploGrep 2: Mitochondrial haplogroup classification in the era of high-throughput sequen-cing // Nucl. Acids Res. 2016. V. 44. № W1. P. W58–W63. https://doi.org/10.1093/nar/gkw233Derenko M., Grzybowski T., Malyarchuk B. et al. Diversity of mitochondrial DNA lineages in South Siberia // Ann. Hum. Genet. 2003. V. 67. № 5. P. 391–411. https://doi.org/10.1046/j.1469-1809.2003.00035.xTorroni A., Sukernik R.I., Schurr T.G. et al. mtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans // Am. J. Hum. Genet. 1993. V. 53. № 3. P. 591–608. https://doi.org/0002-9297/93/5303-0003$02.00Starikovskaya Y.B., Sukernik R.I., Schurr T.G. et al. mtDNA diversity in Chukchi and Siberian Eskimos: Implications for the genetic history of Ancient Beringia and the peopling of the New World // Am. J. Hum. Genet. 1998. V. 63. № 5. P. 1473–1491. https://doi.org/10.1086/302087Derenko M., Malyarchuk B., Grzybowski T. et al. Phylogeographic analysis of mitochondrial DNA in northern Asian populations // Am. J. Hum. Genet. 2007. V. 81. № 5. P. 1025–1041. https://doi.org/10.1086/522933Kumar S., Bellis C., Zlojutro M. et al. Large scale mitochondrial sequencing in Mexican Americans suggests a reappraisal of Native American origins // BMC Evol. Biol. 2011. V. 11. P. 293. https://doi.org/10.1186/1471-2148-11-293Schönherr S., Weissensteiner H., Kronenberg F., Forer L. Haplogrep 3 – an interactive haplogroup classification and analysis platform // Nucl. Acids Res. 2023. V. 51. № W1. P. W263–W268. https://doi.org/10.1093/nar/gkad284Soares P., Ermini L., Thomson N. et al. Correcting for purifying selection: An improved human mitochondrial molecular clock // Am. J. Hum. Genet. 2009. V. 84 № 6. P. 740–759. https://doi.org/10.1016/j.ajhg.2009.05.001López-Bigas N., Rabionet R., Martinez E. et al. Mutations in the mitochondrial tRNA Ser(UCN) and in the GJB2 (connexin 26) gene are not modifiers of the age at onset or severity of hearing loss in Spanish patients with the 12S rRNA A1555G mutation // Am. J. Hum. Genet. 2000. V. 66. № 4. P. 1465–1467. https://doi.org/10.1086/302870Achilli A., Rengo C., Magri C. et al. The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool // Am. J. Hum. Genet. 2004. V. 75. № 5. P. 910–918. https://doi.org/10.1086/425590.Derbeneva O., Starikovskaya E., Wallace D., Suker- nik R.I. Traces of early Eurasians in the Mansi of northwest Siberia revealed by mitochondrial DNA analysis // Am. J. Hum. Genet. 2002. V. 70. № 4. P. 1009–1014. https://doi.org/10.1086/339524Derenko M., Grzybowski T., Malyarchuk B. et al. Diversity of mitochondrial DNA lineages in South Siberia // Ann. Hum. Genet. 2003. V. 67. № 5. P. 391–411. https://doi.org/10.1046/j.1469-1809.2003.00035.xDerenko M., Denisova G., Dambueva I. et al. Mitogenomics of modern Mongolic-speaking populations // Mol. Genet. Genomics. 2022. V. 297. № 1. P. 47–62. https://doi.org/10.1007/s00438-021-01830-wSukernik R., Volodko N., Mazunin I. et al. Mitochondrial genome diversity in the Tubalar, Even, and Ulchi: Сontribution to prehistory of native Siberians and their affinities to Native Americans // Am. J. Phys. Anthropol. 2012. V. 148. № 1. P. 123–138. https://doi.org/10.1002/ajpa.22050Губина М.А., Бабенко В.Н., Бацевич В.А. и др. Полиморфизм митохондриальной ДНК и шести генов ядерного генома в популяции амурских эвенков // Генетика. 2022. Т. 58. № 1. С. 52–67. https://doi.org/10.31857/S0016675822010039Cardinali I., Bodner M., Capodiferro M.R. et al. Mitochondrial DNA footprints from western eurasia in Modern Mongolia // Front. Genet. 2022. V. 12. https://doi.org/10.3389/fgene.2021.819337Derenko M., Malyarchuk B., Bahmanimehr A. et al. Complete mitochondrial DNA diversity in Iranians // PLoS One. 2013. V. 8. № 11. https://doi.org/10.1371/journal.pone.0080673Irwin J.A., Ikramov A., Saunier J. et al. The mtDNA composition of Uzbekistan: A microcosm of Central Asian patterns // Int. J. Legal Med. 2010. V. 124(3). P. 195–204. https://doi.org/10.1007/s00414-009-0406-zAskapuli A., Vilar M., Garcia-Ortiz H. et al. Kazak mitochondrial genomes provide insights into the human population history of Central Eurasia // PLoS One. 2022. V. 17. № 11. https://doi.org/10.1371/journal.pone.0277771Liu J., Wang L.D., Sun Y.B. et al. Deciphering the signature of selective constraints on cancerous mitochondrial genome // Mol. Biol. Evol. 2012. V. 29. № 4. P. 1255–1261. https://doi.org/10.1093/molbev/msr290Lin M., Trejaut J.A. Diversity and distribution of mitochondrial DNA in non-Austronesian-speaking Taiwanese individuals // Hum. Genome Var. 2023. V. 10. № 1. P. 2. https://doi.org/10.1038/s41439-022-00228-3Zheng H.X., Yan S., Qin Z.D. et al. Major population expansion of East Asians began before neolithic time: Evidence of mtDNA genomes // PLoS One. 2011. V. 6. № 10. P .e25835. https://doi.org/10.1371/journal.pone.0025835Li Y.C., Ye W.J., Jiang C.G. et al. River Valleys shaped the maternal genetic landscape of Han Chinese // Mol. Biol. Evol. 2019. V. 36. № 8. P. 1643–1652. https://doi.org/10.1093/molbev/msz072Wang C.Z., Yu X.E., Shi M.S. et al. Whole mitochondrial genome analysis of the Daur ethnic minority from Hulunbuir in the Inner Mongolia Autonomous Region of China // BMC Ecol. Evo. 2022. V. 22. P. 66. https://doi.org/10.1186/s12862-022-02019-4Tanaka M., Cabrera V.M., González A.M. et al. Mitochondrial genome variation in eastern Asia and the peopling of Japan // Genome Res. 2004. V. 14. № 10A. P. 1832–1850. https://doi.org/10.1101/gr.2286304Yamamoto K., Sakaue S., Matsuda K. et al. Genetic and phenotypic landscape of the mitochondrial genome in the Japanese population // Commun. Biol. 2020. V. 3. № 1. P. 104. https://doi.org/10.1038/s42003-020-0812-9Duong N.T., Macholdt E., Ton N.D. et al. Complete human mtDNA genome sequences from Vietnam and the phylogeography of Mainland Southeast Asia // Sci. Rep. 2018. V. 8. № 1. P. 11651. https://doi.org/10.1038/s41598-018-29989-0Kutanan W., Shoocongdej R., Srikummool M. et al. Cultural variation impacts paternal and maternal genetic lineages of the Hmong-Mien and Sino-Tibetan groups from Thailand. // Eur. J. Hum. Genet. 2020. V. 28. № 11. P. 1563–1579. https://doi.org/10.1038/s41431-020-0693-xKutanan W., Kampuansai J., Brunelli A. et al. New insights from Thailand into the maternal genetic history of Mainland Southeast Asia // Eur. J. Hum. Genet. 2018. V. 26. № 6. P. 898–911. https://doi.org/10.1038/s41431-018-0113-7Kutanan W., Kampuansai J., Srikummool M. et al. Complete mitochondrial genomes of Thai and Lao populations indicate an ancient origin of Austroasiatic groups and demic diffusion in the spread of Tai-Kadai languages // Hum. Genet. 2017. V. 136. № 1. P. 85–98. https://doi.org/10.1007/s00439-016-1742-yJaisamut K., Pitiwararom R., Sukawutthiya P. et al. Unraveling the mitochondrial phylogenetic landscape of Thailand reveals complex admixture and demogra- phic dynamics // Sci. Rep. 2023. V. 13. P. 20396. https://doi.org/10.1038/s41598-023-47762-wSummerer M., Horst J., Erhart G. et al. Large-scale mitochondrial DNA analysis in Southeast Asia reveals evolutionary effects of cultural isolation in the multi-ethnic population of Myanmar // BMC Evol. Biol. 2014. V. 28. № 14. P. 17. https://doi.org/10.1186/1471-2148-14-17Bodner M., Perego U.A., Gomez J.E. et al. The mitochondrial DNA landscape of modern Mexico // Genes (Basel). 2021. V. 12. № 9. P. 1453. https://doi.org/10.3390/genes12091453Simão F., Strobl C., Vullo C. et al. The maternal inheritance of Alto Paraná revealed by full mitogenome sequences // Forensic Sci. Int. Genet. 2019. V. 39. P. 66–72. https://doi.org/10.1016/j.fsigen.2018.12.007Zhu Y., Li Q., Chen Z. et al. Mitochondrial haplotype and phenotype of 13 Chinese families may suggest multi-original evolution of mitochondrial C1494T mutation // Mitochondrion. 2009. V. 9. № 6. P. 418–428. https://doi.org/10.1016/j.mito.2009.07.006Lu J., Li Z., Zhu Y. et al. Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss // Mitochondrion. 2010. V. 10. № 4. P. 380–390. https://doi.org/10.1016/j.mito.2010.01.007.Yang X.L., Bai-Cheng X., Chen X.J. et al. Common molecular etiology of patients with nonsyndromic hearing loss in Tibetan, Tu nationality, and Mongolian patients in the northwest of China // Acta Otolaryngol. 2013. V. 133. № 9. P. 930–934. https://doi.org/10.3109/00016489.2013.795288Ma Y., Xiao Y., Bai X. et al. GJB2, SLC26A4, and mitochondrial DNA 12S rRNA hot-spots in 156 subjects with non-syndromic hearing loss in Tengzhou, China // Acta Otolaryngol. 2016. V. 136. P. 800–805. https://doi.org/10.3109/00016489.2016.1164893Zhou Y., Li C., Li M. et al. Mutation analysis of common deafness genes among 1,201 patients with non-syndromic hearing loss in Shanxi Province // Mol. Genet. Genomic Med. 2019. V. 7. № 3. P. e537. https://doi.org/10.1002/mgg3.537Ming L., Wang Y., Lu W., Sun T. A mutational analysis of GJB2, SLC26A4, MT-RNA1, and GJB3 in children with nonsyndromic hearing loss in the Henan province of China // Genet. Test. Mol. Biomarkers. 2019. V. 23. № 1. P. 51–56. https://doi.org/10.1089/gtmb.2018.0146Gao Z., Yuan Y.S. Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: an observational study // Medicine (Baltimore). 2020. V. 99. № 13. P. e19373. https://doi.org/10.1097/MD.0000000000019373Ding Y., Lang J., Zhang J. et al. Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method // Biosci Rep. 2020. V. 40. № 5. https://doi.org/10.1042/BSR20200778Duan S., Guo Y., Chen X., Li Y. Genetic mutations in patients with nonsyndromic hearing impairment of minority and Han Chinese ethnicities in Qinghai, China // J. Int. Med. Res. 2021. V. 49. № 4. https://doi.org/10.1177/03000605211000892Wang Y., Chen W., Liu Z. et al. Comparison of the mutation spectrum of common deafness-causing genes in 509 patients with nonsyndromic hearing loss in 4 different areas of China by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry // J. Int. Adv. Otol. 2021. V. 17. № 6. P. 492–499. https://doi.org/10.5152/iao.2021.21086Dai Q., Dai W., Wang D. et al. Molecular screening of patients with profound hearing loss from Chengdu, China // Acta Otolaryngol. 2022. V. 142. № 1. P. 57–60. https://doi.org/10.1080/00016489.2021.2014564Ma P., Zhou B., Kang Q. et al. Mutation spectrum of hearing loss patients in Northwest China: identification of 20 novel variants // Mol. Genet. Genomic Med. 2024. V. 12. № 6. P. e2434. https://doi.org/10.1002/mgg3.2434Yano T., Nishio S.Y., Usami S. Deafness Gene Study Consortium. Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening // J. Hum. Genet. 2014. V. 59. № 2. P. 100–106. https://doi.org/10.1038/jhg.2013.128Bae J.W., Lee K.Y., Choi S.Y. et al. Molecular analysis of mitochondrial gene mutations in Korean patients with nonsyndromic hearing loss // Int. J. Mol. Med. 2008. V. 22. № 2. P. 175–180. https://doi.org/10.3892/ijmm_00000005Montazer Zohour M., Tabatabaiefar M.A., Dehkordi F.A. et al. Large-scale screening of mitochondrial DNA mutations among Iranian patients with prelingual nonsyndromic hearing impairment // Genet. Test. Mol. Biomarkers. 2012. V. 16. № 4. P. 271–278. https://doi.org/10.1089/gtmb.2011.0176Moassass F., Al-Halabi B., Nweder M.S., Al-Achkar W. Investigation of the mtDNA mutations in Syrian families with non-syndromic sensorineural hearing loss // Int. J. Pediatr. Otorhinolaryngol. 2018. V. 113. P. 110–114. https://doi.org/10.1016/j.ijporl.2018.07.028Yehya A., Al-Trad B., Bani-Hmoud M., Rababa'h A.M. Pharmacogenetic screening of A1555G and C1494T mitochondrial mutations and the use of ototoxic drugs among Jordanians // Eur. Rev. Med. Pharmacol. Sci. 2021. V. 25. № 18. P. 5684–5689. https://doi.org/10.26355/eurrev_202109_26787Rodríguez-Ballesteros M., Olarte M., Aguirre L.A. et al. Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndro- mic hearing loss caused by the 1494C->T mutation in the mitochondrial 12S rRNA gene // J. Med. Genet. 2006. V. 43. № 11. P. e54. https://doi.org/10.1136/jmg.2006.042440Sukarova Stefanovska E., Cakar M., Filipce I., Plaseska Karanfilska D. Genetics of non-syndromic hearing loss in the Republic of Macedonia // Balkan J. Med. Genet. 2012. V. 15(Suppl). P. 57–59. https://doi.org/10.2478/v10034-012-0020-0Mkaouar-Rebai E., Tlili A., Masmoudi S. et al. New polymorphic mtDNA restriction site in the 12S rRNA gene detected in Tunisian patients with non-syndro-mic hearing loss // Biochem. Biophys. Res. Commun. 2008. V. 369. № 3. P. 849–852. https://doi.org/10.1016/j.bbrc.2008.02.107