ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМПymj-1856Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHЭкстремально высокая частота гетерозиготных носителей аутосомно-рецессивной глухоты 1А типа в Восточной Сибири, сопоставимая с частотой гетерозиготного носительства серповидно-клеточной анемии в АфрикеExtremely high frequency of heterozygous carriers of an autosomal recessive deafness 1A type in Eastern Siberia, comparable with the frequency of heterozygous carriers of sickle cell anemia in AfricaБарашковН. А.BarashkovN. A.

Барашков Николай Алексеевич – к.б.н., н.с., с.н.с.

Barashkov Nikolai Alexeevich- PhD, Researcher, Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel. / Fax: 8-(4112)-32-19-81

СоловьевА. В.SolovyevA. V.

Соловьев Айсен Васильевич – инженер-исследователь

Solovyev Aisen Vasilievich - Research Engineer, Research Laboratory of Molecular Biology, Institute of Natural Sciences

677010, st. Kulakovskogo, 36, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8- (4112) 49-68-42

ТерютинФ. М.TeryutinF. M.

Терютин Федор Михайлович – м.н.с., с.н.с.

Teryutin Fyodor Mikhailovich- Junior Researcher, Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) -32-14-73

СоловьеваН. А.SolovyovaN. A.

Соловьева Наталья Алексеевна – к.м.н., м.н.с., с.н.с.

Solovyova Natalia Alexeevna - PhD, Associate Researcher, Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Off. tel. / fax: 8-(4112) -32-19-81

ПшенниковаВ. Г.PshennikovaV. G.

Пшенникова Вера Геннадиевна – лаб.- исслед., м.н.с., аспирант

Pshennikova Vera Gennad’evna - Research Assistant, Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel. / fax: 8-(4112)-32-19-81

КларовЛ. А.ClarovL. A.

Кларов Леонид Александрович – зав. отделением

Clarov Leonid Alexandrovich - head of the Magnetic Resonance Imaging

677005, Pyotr Alexeyev Str. 83, Yakutsk, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) 43-24-29

СидороваО. Г.SidorovaO. G.

Сидорова Оксана Гаврильевна – м.н.с.

Sidorova Oksana Gavrilevna - Junior Researcher, Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) -32-14-73

ГригорьеваЛ. В.GrigorievaL. V.

Григорьева Лена Валерьевна – к.м.н., зав. лаб.

Grigorieva Lena Valer’evna - MD, PhD, Head of the Laboratory of Immunopathology

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel. / Fax: 8-(4112) -32-19-81

РомановГ. П.RomanovG. P.

Романов Георгий Прокопьевич – лаб.-исслед.

Romanov Georgy Prokopievich - Research Assistant, Research Laboratory of Molecular Biology, Institute of Natural Sciences

677010, st. Kulakovskogo 36, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8- (4112) 49-68-42

ГотовцевН. Н.GotovtsevN. N.

Готовцев Ньургун Наумович – студент

Gotovtsev Nyurgun Naumovich - a student of the Institute of Natural Sciences

677000, st. Kulakovskogo , 48, Yakutsk, Republic of Sakha (Yakutia)

СаввиноваК. Е.SavvinovaK. E.

Саввинова Кюнней Егоровна – студент

Savvinova Kyunney Egorovna - a student of the Institute of Natural Sciences

677000, st. Kulakovskogo, 48, Yakutsk, Republic of Sakha (Yakutia)

НаходкинС. С.NakhodkinS. S.

Находкин Сергей Сергеевич – м.н.с., аспирант

Nakhodkin Sergey Sergeevich - Junior Researcher, Research Laboratory of Molecular Biology, Institute of Natural Sciences

677010, st. Kulakovskogo, 36, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8- (4112) 49-68-42

КожевниковА. А.KozhevnikovA. A.

Кожевников Александр Александрович – директор Респ. центра проф. Патологии

Kozhevnikov Alexander Alexandrovich - Director of the National Center of occupational diseases

677005, Pyotr Alexeyev, 83, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) 43-24-29

ВасильеваЛ. М.VasilyevaL. M.

Васильева Лена Максимовна – сурдопедагог Сурдологопедич. Центра

Vasilyeva Lena Maksimovna - surdopedagog, Republican Surdologopedical Center

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel . : 8-(4112) 39-53-20

ФедотоваЭ. Е.FedotovaE. E.

Федотова Эльвира Егоровна – к.м.н., зав. Сурдологопедич. Центром

Fedotova Elvira Egorovna - MD, a physician audiologist, otolaryngologist, chief out-of-staff specialist audiologist of the Ministry of Health of the Republic of Sakha ( Yakutia), Head of the Republican surdologopedichal Center

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) 39-53-20

ПакМ. В.PakM. V.

Пак Мария Владимировна – аспирант

Pak Maria Vladimirovna - graduate student

677010, st. Oyunskiy, 27, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) 36-30-46

ЛехановаС. Н.LekhanovaS. N.

Леханова Саргылана Николаевна – к.м.н., доцент

Lekhanova Sargylana Nikolaevna - PhD, Associate Professor

677010, st. Oyunskiy, 27, Yakutsk, Republic of Sakha (Yakutia), Office tel.: 8-(4112) 36-30-46

КононоваС. К.KononovaS. K.

Кононова Сардана Кононовна – к.б.н., с.н.с., с.н.с.

Kononova Sardana Kononovna - PhD, Senior Researcher, Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4 Yakutsk, Republic of Sakha (Yakutia), tel / fax: (4112) 32-19-81

РафаиловА. М.RaphailovA. M.

Рафаилов Адюм Михайлович – к.б.н., доцент

Raphailov Adyum Mikhajlovich - PhD, associate professor, Department of Biology, Faculty of Biology and Geography

677010, st. Kulakovskogo , 48, Yakutsk, Republic of Sakha (Yakutia), Tel.: 8- (4112) 49-68-42

АлексеевА. Н.AlekseevA. N.

Alekseev Anatoly Nikolaevich- PhD, Professor, Director

677007, Yakutsk, st. Petrovsky, 1, Republic of Sakha (Yakutia), tel / fax : 8 ( 4112 ) 39-00-36

ПосухО. Л.PosukhO. L.

Посух Ольга Леонидовна – к.б.н., с.н.с.;

Доцент

Posukh Olga Leonidovna - PhD, Senior Scientist, Laboratory of Human Molecular Genetics

Novosibirsk, 630090, Lavrentiev avenue, 10, tel.: 8 (383) 363-49-44 (2210), Fax: 8-(383) 333-12-78

ДжемилеваЛ. У.DzhemilevaL. U.

Джемилева Лиля Усеиновна – д.м.н., с.н.с

Dzhemileva Lily Useinovna - Ph.D., Senior Scientist, Laboratory of Human Molecular Genetics

450054, pr October, 71, Ufa,Russia. tel / fax : 8-( 3472 ) 35-60-88

ХуснутдиноваЭ. К.KhusnutdinovaE. K.

Хуснутдинова Эльза Камилевна – д.б.н., проф., зав. отделом, зав. кафедрой

Khusnutdinova Elsa Kamilevna - Ph.D., Professor, Head of Genomics Dep.

450054 , pr October, 71 Ufa, Russia. tel / fax : 8-( 3472 ) 35-60- 88

ФедороваС. А.FedorovaS. A.

Федорова Сардана Аркадьевна – д.б.н., зав.лаб., зав. лаб.

Fedorova Sardana Arkadevna - Ph.D., Head of Laboratory of Molecular Genetics

677010, Sergelyakhskoe highway, 4, Yakutsk, Republic of Sakha (Yakutia). Office tel. / Fax: 8-(4112) 32-19-81

Якутский НЦ КМП СО РАМН; СВФУ им. М.К. АммосоваРоссияFGBU "Yakut Scientific Center of Complex Medical Problems", Siberian Branch of the Russian Academy of Medical SciencesRussian FederationСВФУРоссияFederal State Autonomous Educational Institution of Higher Professional Education "North- Eastern Federal University named after M.K. Ammosov"Russian FederationЯкутский НЦ КМП СО РАМН; СВФУРоссияFGBU "Yakut Scientific Center of Complex Medical Problems", Siberian Branch of the Russian Academy of Medical SciencesRussian FederationГБУ РС(Я) РБ№2-ЦЭМПРоссияState Budget Institution of the Republic of Sakha (Yakutia) Republic hospital number 2 - Center for Emergency MedicineRussian FederationЯкутский НЦ КМП СО РАМНРоссияFGBU "Yakut Scientific Center of Complex Medical Problems", Siberian Branch of the Russian Academy of Medical SciencesRussian FederationЯкутский НЦ КМП СО РАМНРоссияFGBU "Yakut Scientific Center of Complex Medical Problems" , Siberian Branch of the Russian Academy of Medical SciencesRussian FederationСВФУРоссияFederal State Autonomous Educational Institution of Higher Professional Education «North- Eastern Federal University named after M.K. Ammosov"Russian FederationГБУ РС(Я) РБ№1-НЦМРоссияState Budget Institution of the Republic of Sakha (Yakutia), Republic hospital number 1 - The National Center of MedicineRussian FederationГБУ РС(Я) РБ№1-НЦМРоссияState Budget Institution of the Republic of Sakha (Yakutia) Republic hospital number 1 - The National Center of MedicineRussian FederationСВФУРоссияMedical Institute, Federal State Autonomous Educational Institution of Higher Professional Education "North- Eastern Federal University named after M.K. Ammosov"Russian FederationСВФУРоссияInstitute of Medicine, Federal State Autonomous Educational Institution of Higher Professional Education "North- Eastern Federal University named after M.K. Ammosov"Russian FederationЯкутский НЦ КМП СО РАМН; СВФУРоссияFederal State Institution "Yakut Scientific Center complex medical problems" the Siberian Branch of the Russian Academy of Medical SciencesRussian FederationFederal State Institution of Science Institute of Humanitarian Research and Indigenous Peoples of the North, Siberian Branch of the Russian Academy of SciencesRussian FederationФГБУН ИЦиГ СО РАН; ФГБОУ ВПО «Новосибирский НИГУ»РоссияFederal State Institution of Science Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesRussian FederationФГБУН ИБГ УНЦ РАНРоссияFederal State Institution of Science Institute of Biochemistry and Genetics, Ufa Scientific Center of the Russian Academy of SciencesRussian FederationФГБОУ ВПО «Башкирский ГУ»РоссияFederal State Institution of Science Institute of Biochemistry and Genetics, Ufa Scientific Center of the Russian Academy of SciencesRussian Federation201305102025042730Copyright © Барашков Н.А., Соловьев А.В., Терютин Ф.М., Соловьева Н.А., Пшенникова В.Г., Кларов Л.А., Сидорова О.Г., Григорьева Л.В., Романов Г.П., Готовцев Н.Н., Саввинова К.Е., Находкин С.С., Кожевников А.А., Васильева Л.М., Федотова Э.Е., Пак М.В., Леханова С.Н., Кононова С.К., Рафаилов А.М., Алексеев А.Н., Посух О.Л., Джемилева Л.У., Хуснутдинова Э.К., Федорова С.А., 20252025Барашков Н.А., Соловьев А.В., Терютин Ф.М., Соловьева Н.А., Пшенникова В.Г., Кларов Л.А., Сидорова О.Г., Григорьева Л.В., Романов Г.П., Готовцев Н.Н., Саввинова К.Е., Находкин С.С., Кожевников А.А., Васильева Л.М., Федотова Э.Е., Пак М.В., Леханова С.Н., Кононова С.К., Рафаилов А.М., Алексеев А.Н., Посух О.Л., Джемилева Л.У., Хуснутдинова Э.К., Федорова С.А.Barashkov N.A., Solovyev A.V., Teryutin F.M., Solovyova N.A., Pshennikova V.G., Clarov L.A., Sidorova O.G., Grigorieva L.V., Romanov G.P., Gotovtsev N.N., Savvinova K.E., Nakhodkin S.S., Kozhevnikov A.A., Vasilyeva L.M., Fedotova E.E., Pak M.V., Lekhanova S.N., Kononova S.K., Raphailov A.M., Alekseev A.N., Posukh O.L., Dzhemileva L.U., Khusnutdinova E.K., Fedorova S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/1856

В работе представлены результаты исследования частоты гетерозиготного носительства мутации IVS1+1G>A гена GJB2, приводящей к аутосомно-рецессивной форме глухоты, у якутов в различных этногеографических группах и в случайной выборке. Экстремально высокая частота гетерозиготного носительства мутации сайта сплайсинга IVS1+1G>A гена GJB2 в популяции якутов сопоставима с частотой гетерозиготного носительства серповидно-клеточной анемии в Африке, что может свидетельствовать о возможном селективном преимуществе носителей данной мутации в условиях субарктического климата.

This study presents data on the carrier frequency of IVS1+1G>A mutation in GJB2 gene, leading to an autosomal recessive form of deafness among various ethno-geographical groups of Yakut population and in a random sample. Extremely high carrier frequency of the splice site IVS1+1G>A mutation in GJB2 gene in the Yakut population is comparable to the carrier frequency of the sickle-cell anemia in Africa, what may indicate a possible selective advantage of carriers of this IVS1+1G>A mutation in a subarctic climate.

аутосомно-рецессивная глухота тип 1АВосточная Сибирьсерповидно-клеточная анемияАфрикаautosomal recessive deafness 1AEastern Siberiasickle-cell anemiaAfricaРабота выполнена при финансовой поддержке грантов РФФИ (11-04-01221-а), (12-04-00342-а), (12- 04-98520-р_восток_а), (12-04-97004- р_поволжье_а), (12-04-31230-мол_а), ФЦП «Научные и научно-педагогические кадры инновационной России» на 2009-2013гг. (№ 16.740.11.0190), (№ 16.740.11.0346), Интеграционного проекта СО РАН № 92. «Этногенез автохтонных народов Сибири и Северной Азии: компаративный, исторический, этносоциальный и геномный анализ», а также гранта Президента Республики Саха (Якутия) им. А.И. Иванова для молодых ученых, специалистов и студентов за 2013 год (РП №79 от 08.02.2013г).This study was supported by the Russian Foundation for Basic Research (11-04-01221-а, 12-04-00342-а, 12-04-98520-r_vostok_a, 12-04-97004-r_povolzhye_a, 12-04-31230-mol_a), Federal Program «Scientific and educational staff for innovative Russia» (#16.740.11.0190, #16.740.11.0346), Integration project of SB RAS № 92 "Ethnogeny of indigenous peoples in Siberia and North Asia: comparative, historical, ethno -social and genomic analysis”, and the Sakha Republic President Grant #79 for Young Researchers for 2013 year (RP #79 08.02.2013).ReferencesБлочная архитектура предкового гаплотипа мутации сайта сплайсинга IVS1+1G>A гена GJB2 (Cx26), в популяции якутов (по данным 7 SNP-маркеров) / А.В. Соловьев, Н.А. Барашков, Л.У. Джемилева [и др.] / Материалы международной конференции «Высокопроизводительное секвенирование в геномике». HSG-2013 Новосибирск, 21-25 июля 2013 г. – C. 81.Block architecture of the ancestral haplotype of the splice site mutation IVS1 +1 G> A gene GJB2 (Cx26), in the Yakut population (as of 7 SNP-markers) / A.V. Soloviev, N.A. Barashkov, L.Y. Dzhemileva [et al.] // International Conference “Highthroughput sequencing in genomics” HGS-2013.- Novosibirsk, Russia, July 21-25.- 2013.- p. 81.Allison A.C. Protection afforded by sicklecell trait against Subtertian malarial infection / A.C. Allison, D. Phil // British Med. J.-1954.- Feb.6.-P. 290-294.Allison A.C. Protection afforded by sicklecell trait against Subtertian malarial infection / A.C. Allison, D. Phil // British Med. J.-1954.- Feb.6.-P. 290-294.Allison A.C. Malaria in Carriers of the SickleCell Trait and in Newborn Children / A.C. Allison // Experimental parasitology.-1957.-Vol.6.-P. 418- 447.Allison A.C. Malaria in Carriers of the SickleCell Trait and in Newborn Children / A.C. Allison // Experimental parasitology.-1957.-Vol.6.-P. 418- 447.An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals / G.A. Lazarin, I.S. Haque, S. Nazareth [et al.] // Genet Med.-2013.-Vol.15.-P. 178-86.An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals / G.A. Lazarin, I.S. Haque, S. Nazareth [et al.] // Genet Med.-2013.-Vol.15.-P. 178-86.Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect / N.A. Barashkov, L.U. Dzhemileva, S.A. Fedorova [et al.] // Journal of Human Genetics.- 2011.-Vol. 56, №8.-P.631-639.Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect / N.A. Barashkov, L.U. Dzhemileva, S.A. Fedorova [et al.] // Journal of Human Genetics.- 2011.-Vol. 56, №8.-P.631-639.Connexin 26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans / L. Zelante, P. Gasparini, X. Estivill [et al.] // Hum. Mol. Genet.- 1997.-Vol. 6.-P. 1605-1609.Connexin 26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans / L. Zelante, P. Gasparini, X. Estivill [et al.] // Hum. Mol. Genet.- 1997.-Vol. 6.-P. 1605-1609.Connexin 26 mutations in hereditary nonsyndromic sensorineural deafness / D.P. Kelsell, J. Dunlop, H.P. Stevens [et al.] // Nature.-1997.- Vol. 387, №6628.-P. 80-83.Connexin 26 mutations in hereditary nonsyndromic sensorineural deafness / D.P. Kelsell, J. Dunlop, H.P. Stevens [et al.] // Nature.-1997.- Vol. 387, №6628.-P. 80-83.Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis / F.B. Piel, A.P. Patil, R.E. Howes [et al.] // Nat Commun.-2010.-DOI: 10.1038/ncomms1104.Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis / F.B. Piel, A.P. Patil, R.E. Howes [et al.] // Nat Commun.-2010.-DOI: 10.1038/ncomms1104.Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical modelbased map and population estimates / F.B. Piel, A.P. Patil, R.E. Howes [et al.] // Lancet.-2013.-Vol. 381.-Р. 142-151.Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical modelbased map and population estimates / F.B. Piel, A.P. Patil, R.E. Howes [et al.] // Lancet.-2013.-Vol. 381.-Р. 142-151.Modell B. Global epidemiology of haemoglobin disorders and derived service indicators / B. Modell, M. Darlison // Bull World Health Organ.-2008.-Vol. 86, №6.-Р. 480-7.Modell B. Global epidemiology of haemoglobin disorders and derived service indicators / B. Modell, M. Darlison // Bull World Health Organ.-2008.-Vol. 86, №6.-Р. 480-7.Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss / P.M. Kelley, D.J. Harris, B.C. Comer [et al.] // Am. J. Hum. Genet.-1998.-Vol. 62, №4.- P. 792-799.Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss / P.M. Kelley, D.J. Harris, B.C. Comer [et al.] // Am. J. Hum. Genet.-1998.-Vol. 62, №4.- P. 792-799.Sirmaci A. The c. IVS1+1G>A mutation in the GJB2 gene is prevalent and large deletions involving the GJB6 gene are not present in the Turkish population / A. Sirmaci, D. Akcayozduman, M. Tekin // Journal of Genetics (Indian academy of sciences).-2006.-Vol. 85, №3.-P.213-216.Sirmaci A. The c. IVS1+1G>A mutation in the GJB2 gene is prevalent and large deletions involving the GJB6 gene are not present in the Turkish population / A. Sirmaci, D. Akcayozduman, M. Tekin // Journal of Genetics (Indian academy of sciences).-2006.-Vol. 85, №3.-P.213-216.Weatherall D.J. Inherited haemoglobin disorders: an increasing global health problem / D.J. Weatherall, J.B. Clegg // Bull World Health Organ.-2001.-Vol. 79, №8.-P.704-12.Weatherall D.J. Inherited haemoglobin disorders: an increasing global health problem / D.J. Weatherall, J.B. Clegg // Bull World Health Organ.-2001.-Vol. 79, №8.-P.704-12.Web site NCBI (OMIM) Web site NCBI (OMIM): (http://omim.org/entry/220290), (http://omim.org/entry/121011).Web site NCBI (OMIM) Web site NCBI (OMIM): (http://omim.org/entry/220290), (http://omim.org/entry/121011).

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