medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.05.3-11medgen-2286Research ArticleНАУЧНЫЙ ОБЗОРREVIEWПервые результаты и перспективы медико-генетических исследований музейных и археологических образцовThe first results and prospects of medical genetic studies of museum and archaeological samplesАндрееваТ. В.AndreevaT. V.

354340 Краснодарский край, федеральная территория «Сириус», пгт. Сириус, Олимпийский пр., д. 1

119991, ГСП-1, г. Москва, ул. Губкина, д. 3

119991, Москва, Ленинские горы, д. 1, стр. 12

1, Olympic prospect., town. Sirius, federal territory “Sirius”, 354340

3, Gubkina st., Moscow, 119333

1, building 12, Leninskiye Gory, Moscow, 119991

andreeva@vigg.ruБыдановА. С.BydanovA. S.

354340 Краснодарский край, федеральная территория «Сириус», пгт. Сириус, Олимпийский пр., д. 1

1, Olympic prospect., town. Sirius, federal territory “Sirius”, 354340

ГусевФ. Е.GusevF. E.

354340 Краснодарский край, федеральная территория «Сириус», пгт. Сириус, Олимпийский пр., д. 1

119991, ГСП-1, г. Москва, ул. Губкина, д. 3

1, Olympic prospect., town. Sirius, federal territory “Sirius”, 354340

3, Gubkina st., Moscow, 119333

РогаевЕ. И.RogaevE. I.

354340 Краснодарский край, федеральная территория «Сириус», пгт. Сириус, Олимпийский пр., д. 1

119991, Москва, Ленинские горы, д. 1, стр. 12

Шрусбери, 01545 США

1, Olympic prospect., town. Sirius, federal territory “Sirius”, 354340

1, building 12, Leninskiye Gory, Moscow, 119991

Worcester, MA 01545, USA

Центр генетики и наук о жизни, АНОО ВО «Научно-технологический университет «Сириус»; Институт общей генетики им. Н.И. Вавилова Российской академии наук; Центр генетики и генетических технологий, Московский государственный университет им. М.В. ЛомоносоваРоссияCenter for Genetics and Life Science, Sirius University of Science and Technology; Vavilov Institute of General Genetics, Russian Academy of Sciences; Center for Genetics and Genetic Technologies, Faculty of Biology, Lomonosov Moscow State UniversityRussian FederationЦентр генетики и наук о жизни, АНОО ВО «Научно-технологический университет «Сириус»РоссияCenter for Genetics and Life Science, Sirius University of Science and TechnologyRussian FederationЦентр генетики и наук о жизни, АНОО ВО «Научно-технологический университет «Сириус»; Институт общей генетики им. Н.И. Вавилова Российской академии наукРоссияCenter for Genetics and Life Science, Sirius University of Science and Technology; Vavilov Institute of General Genetics, Russian Academy of SciencesRussian FederationЦентр генетики и наук о жизни, АНОО ВО «Научно-технологический университет «Сириус»; Центр генетики и генетических технологий, Московский государственный университет им. М.В. Ломоносова; Медицинская школа Чан Массачусетского университета, департамент психиатрииРоссияCenter for Genetics and Life Science, Sirius University of Science and Technology; Center for Genetics and Genetic Technologies, Faculty of Biology, Lomonosov Moscow State University; Department of Psychiatry, UMass Chan Medical SchoolRussian Federation202327072023225311Copyright © Андреева Т.В., Быданов А.С., Гусев Ф.Е., Рогаев Е.И., 20232023Андреева Т.В., Быданов А.С., Гусев Ф.Е., Рогаев Е.И.Andreeva T.V., Bydanov A.S., Gusev F.E., Rogaev E.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2286

Несмотря на впечатляющее успехи археогенетики, медико-генетическая история древнего народонаселения остаётся мало разработанной областью. Работы по исследованию древних геномов отдельных индивидов или групп людей, живших в различные исторические и доисторические периоды, как правило, связаны с изучением их эволюционной и популяционной истории, происхождения и миграций. В обзоре мы рассматриваем перспективность нового направления – патогенетики древних людей. Для корректной медико-генетической интерпретации геномных данных необходимы критерии достоверности, учитывающие особенности древней ДНК: плохую сохранность ДНК, контаминацию современной ДНК человека и микробной ДНК и особенно химические модификации, накапливающиеся в ДНК. Такие модификации ведут к появлению с высокой частотой так называемых “постмортальных” мутаций в древних геномах.  К настоящему времени есть лишь единичные работы, посвященные выявлению генов менделирующих заболеваний при анализе древней ДНК, которые будут рассмотрены в обзоре.

Despite the impressive achievements of paleogenetics, the medical and genetic history of ancient populations has yet to be explored in detail. The vast majority of studies on ancient individuals or groups of people who lived in various historical and prehistoric periods focus on their evolutionary and population history, their origin and migrations. Here we discuss the prospects of a new direction – the pathogenetics of ancient people. For correct medical and genetic interpretation of genomic data, reliability criteria have to be established taking into account the specific features of ancient DNA: poor DNA preservation, contamination with modern human and microbial DNA, and, especially, chemical modifications accumulating in DNA. In the sequencing data of ancient genomes these modifications manifest themselves with high frequency in a form of so-called “postmortem” mutations. To date, only a few studies are devoted to the identification of genes of mendelian diseases using ancient DNA, which are discussed in this review.

древняя ДНКглубокое секвенированиепатогенные мутациипалеогеномикаancient DNANGSpathogenic mutationspaleogenomicsРабота выполнена при финансовой поддержке Минобрнауки России (системный номер 075-10-2020-116, номер гранта 13.1902.21.0023).The work was supported financially by the Ministry of Science and Higher Education of the Russian Federation (system number 075-10-2020-116, grant number 13.1902.21.0023).ReferencesMalyarchuk A.B., Andreeva T .V., Kuznetsova I.L. et al. Genomics of Ancient Pathogens: First Advances and Prospects. Biochem 2022 873. 2022 Mar 11;87(3):242–58.Malyarchuk A.B., Andreeva T .V., Kuznetsova I.L. et al. Genomics of Ancient Pathogens: First Advances and Prospects. Biochem 2022 873. 2022 Mar 11;87(3):242–58.Андреева Т.В., Малярчук А.Б., Сошкина А.Д. и др. Методология выделения древней ДНК из костной ткани для геномного анализа: подходы и практические рекомендации. Генетика. 2022;58(9):979–98.Andreeva T.V., Malyarchuk A.B., Soshkina A.D., et al. Metodologiya vydeleniya drevney DNK iz kostnoy tkani dlya genomnogo analiza: podkhody i prakticheskiye rekomendatsii [Methodologies of ancient DNA extraction from bones for genomic analysis: approaches and practical recommendations]. Genetika [Genetics]. 2022;58(9):979–98. (In Russ.)Meyer M., Fu Q., Aximu-Petri A. et al. A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature. 2014;505(7483):403–6.Meyer M., Fu Q., Aximu-Petri A. et al. A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature. 2014;505(7483):403–6.Mouttham N., Klunk J., Kuch M. et al. Surveying the repair of ancient dna from bones via high-throughput sequencing. Biotechniques. 2015;59(1):19–25.Mouttham N., Klunk J., Kuch M. et al. Surveying the repair of ancient dna from bones via high-throughput sequencing. Biotechniques. 2015;59(1):19–25.Andreeva T.V., Manakhov A.D., Kunizheva S.S., Rogaev E.I. Genetic evidence of authenticity of a hair shaft relic from the portrait of tsesarevich Alexei, the son of the last Russian Emperor. Biochem. 2021;86(12).Andreeva T.V., Manakhov A.D., Kunizheva S.S., Rogaev E.I. Genetic evidence of authenticity of a hair shaft relic from the portrait of tsesarevich Alexei, the son of the last Russian Emperor. Biochem. 2021;86(12).Pusch C.M., Broghammer M., Nicholson G.J. et al. PCR-Induced Sequence Alterations Hamper the Typing of Prehistoric Bone Samples for Diagnostic Achondroplasia Mutations. Mol Biol Evol. 2004 Nov 1;21(11):2005–11.Pusch C.M., Broghammer M., Nicholson G.J. et al. PCR-Induced Sequence Alterations Hamper the Typing of Prehistoric Bone Samples for Diagnostic Achondroplasia Mutations. Mol Biol Evol. 2004 Nov 1;21(11):2005–11.Robinson P., Zemo jtel T. Integrative genomics viewer (IGV): Visualizing alignments and variants. In: Computational Exome and Genome Analysis. 2018. p. 233–45.Robinson P., Zemo jtel T. Integrative genomics viewer (IGV): Visualizing alignments and variants. In: Computational Exome and Genome Analysis. 2018. p. 233–45.Jónsson H., Ginolhac A., Schubert M. et al. mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters. Bioinformatics. 2013 Jul;29(13):1682–4.Jónsson H., Ginolhac A., Schubert M. et al. mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters. Bioinformatics. 2013 Jul;29(13):1682–4.Boer L.L., Naue J., De Rooy L., Oostra R.J. Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton. Genes 2017, Vol 8, Page 214. 2017 Aug 29;8(9):214.Boer L.L., Naue J., De Rooy L., Oostra R.J. Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton. Genes 2017, Vol 8, Page 214. 2017 Aug 29;8(9):214.Gansauge M.T., Gerber T., Glocke I .et al. Single-stranded DNA library preparation from highly degraded DNA using T4 DNA ligase. Nucleic Acids Res. 2017 Jun 2;45(10):e79.Gansauge M.T., Gerber T., Glocke I .et al. Single-stranded DNA library preparation from highly degraded DNA using T4 DNA ligase. Nucleic Acids Res. 2017 Jun 2;45(10):e79.Рыжкова О.П., Кардымон О.Л., Прохорчук Е.Б. и др. Руководство по интерпретации данных последовательности ДНК человека, полученных методами массового параллельного секвенирования (MPS). Медицинская Генетика. 2019;18(2): 3–23.Ryzhkova O.P., Kardymon O.L., Prohorchuk E.B., et al. Rukovodstvo po interpretatsii dannykh posledovatel’nosti DNK cheloveka, poluchennykh metodami massovogo parallel’nogo sekvenirovaniya (MPS) (redaktsiya 2018, versiya 2) [Guidelines for the interpretation of massive parallel sequencing variants (update 2018, v2)]. Meditsinskaya genetika [Medical Genetics]. 2019;18(2):3-23. (In Russ.) https://doi.org/10.25557/2073-7998.2019.02.3-23Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May 8;17(5):405–24.Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May 8;17(5):405–24.Hajdinjak M., Fu Q., Hübner A. et al. Reconstructing the genetic history of late Neanderthals. Nature. 2018;555(7698):652–6.Hajdinjak M., Fu Q., Hübner A. et al. Reconstructing the genetic history of late Neanderthals. Nature. 2018;555(7698):652–6.Fu Q., Hajdinjak M., Moldovan O.T. et al. An early modern human from Romania with a recent Neanderthal ancestor. Nat 2015 5247564. 2015 Jun 22;524(7564):216–9.Fu Q., Hajdinjak M., Moldovan O.T. et al. An early modern human from Romania with a recent Neanderthal ancestor. Nat 2015 5247564. 2015 Jun 22;524(7564):216–9.Lazaridis I., Alpaslan-Roodenberg S., Acar A. et al. Ancient DNA from Mesopotamia suggests distinct Pre-Pottery and Pottery Neolithic migrations into Anatolia. Science (80- ). 2022 Aug 26;377(6609):982–7.Lazaridis I., Alpaslan-Roodenberg S., Acar A. et al. Ancient DNA from Mesopotamia suggests distinct Pre-Pottery and Pottery Neolithic migrations into Anatolia. Science (80- ). 2022 Aug 26;377(6609):982–7.Chintalapati M., Patterson N., Moorjani P. The spatiotemporal patterns of major human admixture events during the European Holocene. Elife. 2022 May 1;11.Chintalapati M., Patterson N., Moorjani P. The spatiotemporal patterns of major human admixture events during the European Holocene. Elife. 2022 May 1;11.Liu Y.C., Hunter-Anderson R., Cheronet O. et al. Ancient DNA reveals five streams of migration into Micronesia and matrilocality in early Pacific seafarers. Science. 2022 Jul 1;377(6601):72–9.Liu Y.C., Hunter-Anderson R., Cheronet O. et al. Ancient DNA reveals five streams of migration into Micronesia and matrilocality in early Pacific seafarers. Science. 2022 Jul 1;377(6601):72–9.Filon D., Faerman M., Smith P., Oppenheim A. Sequence analysis reveals a β–thalassaemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. Nat Genet 1995 94. 1995;9(4):365–8.Filon D., Faerman M., Smith P., Oppenheim A. Sequence analysis reveals a β–thalassaemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. Nat Genet 1995 94. 1995;9(4):365–8.Rogaev E.I., Grigorenko A.P., Faskhutdinova G. et al. Genotype analysis identifies the cause of the “royal disease.” Science. 2009 Nov 6;326(5954):817.Rogaev E.I., Grigorenko A.P., Faskhutdinova G. et al. Genotype analysis identifies the cause of the “royal disease.” Science. 2009 Nov 6;326(5954):817.Jackson I., Mattiangeli V., Cassidy L.M. et al. Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard. Eur J Hum Genet. 2022;Jackson I., Mattiangeli V., Cassidy L.M. et al. Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard. Eur J Hum Genet. 2022;Beckers A., Fernandes D., Fina F. et al. Paleogenetic study of ancient DNA suggestive of X-linked acrogigantism. Endocr Relat Cancer. 2017 Feb 1;24(2):L17–20.Beckers A., Fernandes D., Fina F. et al. Paleogenetic study of ancient DNA suggestive of X-linked acrogigantism. Endocr Relat Cancer. 2017 Feb 1;24(2):L17–20.Marchetti A., Pellegrini S., Bevilacqua G., Fornaciari G. K-RAS mutation in the tumour of Ferrante I of Aragon, King of Naples. Lancet. 1996 May 4;347(9010):1272.Marchetti A., Pellegrini S., Bevilacqua G., Fornaciari G. K-RAS mutation in the tumour of Ferrante I of Aragon, King of Naples. Lancet. 1996 May 4;347(9010):1272.Iadarola B., Lavezzari D., Modi A. et al. Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291-1329 CE) indicates the first known case of late-onset Pompe disease. Sci Rep. 2021 Dec 1;11(1).Iadarola B., Lavezzari D., Modi A. et al. Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291-1329 CE) indicates the first known case of late-onset Pompe disease. Sci Rep. 2021 Dec 1;11(1).Cassidy L.M., Maoldúin R., Kador T. et al. A dynastic elite in monumental Neolithic society. Nat 2020 5827812. 2020 Jun 17;582(7812):384–8.Cassidy L.M., Maoldúin R., Kador T. et al. A dynastic elite in monumental Neolithic society. Nat 2020 5827812. 2020 Jun 17;582(7812):384–8.Gnecchi-Ruscone G.A., Khussainova E., Kahbatkyzy N. et al. Ancient genomic time transect from the Central Asian Steppe unravels the history of the Scythians. Sci Adv. 2021 Mar 1;7(13):4414–40.Gnecchi-Ruscone G.A., Khussainova E., Kahbatkyzy N. et al. Ancient genomic time transect from the Central Asian Steppe unravels the history of the Scythians. Sci Adv. 2021 Mar 1;7(13):4414–40.Viganó C., Haas C., Rühli F.J., Bouwman A. 2,000 Year old β-thalassemia case in Sardinia suggests malaria was endemic by the Roman period. Am J Phys Anthropol. 2017 Oct 1;164(2):362–70.Viganó C., Haas C., Rühli F.J., Bouwman A. 2,000 Year old β-thalassemia case in Sardinia suggests malaria was endemic by the Roman period. Am J Phys Anthropol. 2017 Oct 1;164(2):362–70.Toncheva D., Marinova M., Borovska .P, Serbezov D. Spatiotemporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA. PLoS One. 2022 Jun 1;17(6):e0269628.Toncheva D., Marinova M., Borovska .P, Serbezov D. Spatiotemporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA. PLoS One. 2022 Jun 1;17(6):e0269628.

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