fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2023-8-2-53-66fcmedicine-715Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL RESEARCHАналитический скрининг полиморфных вариантов генов 20S протеасомы при планировании исследования патогенетических эффектов модификации посттрансляционного процессинга NFKB1Analytical screening of polymorphic variants of 20S proteasome genes when planning a study of pathogenetic effects of modification of NFKB1 post-translational processinghttps://orcid.org/0000-0001-9952-7854МейерА. В.MeyerA. V.

Мейер Алина Викторовна, кандидат биологических наук, доцент кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Mrs. Alina V. Meyer, PhD (Biology), Associate Professor of the Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

shapo-alina@yandex.ruhttps://orcid.org/0000-0002-7945-566XУльяноваМ. В.UlyanovaM. V.

Ульянова Марина Владиславовна, кандидат биологических наук, доцент кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Mrs. Marina V. Ulyanova, PhD (Biology), Associate Professor of the Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0002-0927-4855ИмекинаД. О.ImekinaD. O.

Имекина Дарья Олеговна, ассистент кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Mrs. Darya O. Imekina, Assistant, Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0002-2527-0790ПадюковаА. Д.PadyukovaA. D.

Падюкова Асия Дамировна, старший лаборант кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Mrs. Asiya D. Padyukova, Senior Assistant, Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0003-4645-7009ТолочкоТ. А.TolochkoT. A.

Толочко Татьяна Андреевна, старший преподаватель кафедры морфологии и судебной медицины

650056, г. Кемерово, ул. Ворошилова, д. 22а

Dr. Tatiana A. Tolochko, MD, Senior Lecturer, Department of Morphology and Forensic Medicine

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0002-5841-6311АстафьеваЕ. А.AstafievaE. A.

Астафьева Евгения Анатольевна, ассистент кафедры морфологии и судебной медицины

650056, г. Кемерово, ул. Ворошилова, д. 22а

Dr. Eugeniya A. Astaf’eva, MD, Assistant, Department of Morphology and Forensic Medicine

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0003-1593-0676ЛавряшинаМ. Б.LavryashinaM. B.

Лавряшина Мария Борисовна, доктор биологических наук, доцент, заведующая кафедрой молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Prof. Marya B. Lavryashina, DSc (Biology), Head of the Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

ФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKemerovo State Medical UniversityRussian Federation202330062023825366Copyright © Мейер А.В., Ульянова М.В., Имекина Д.О., Падюкова А.Д., Толочко Т.А., Астафьева Е.А., Лавряшина М.Б., 20232023Мейер А.В., Ульянова М.В., Имекина Д.О., Падюкова А.Д., Толочко Т.А., Астафьева Е.А., Лавряшина М.Б.Meyer A.V., Ulyanova M.V., Imekina D.O., Padyukova A.D., Tolochko T.A., Astafieva E.A., Lavryashina M.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/715

Цель. Формирование панели полиморфных вариантов генов 20S протеасомы, потенциально значимых для исследования в качестве факторов-модификаторов баланса р105/р50 NFKB1.Материалы и методы. Определение перспективных для целей исследования генов, кодирующих белки мультисубъединичного протеасомного комплекса, проводилось на основе информационного поиска с использованием ресурсов eLIBRARY и PubMed. Источником информации для формирования панели полиморфных вариантов генов (SNP, single nucleotide polymorphism) послужил геномный браузер Ensembl, http://www.ensembl.org. Структура генов описана по данным NCBI (Gene databases, http://www.ncbi.nlm.nih.gov/gene).Наполнение панели осуществлено с учетом минорной аллельной частоты в популяции (MAF), локализации SNP в структуре гена и наличия данных о связи с многофакторными заболеваниями и иными эффектами. Для расчёта генетических расстояний между популяциями применялся метод сравнения популяций по частотам аллелей полиморфных маркёров, предложенный Неем, полученные матрицы проиллюстрированы методом многомерного шкалирования в пространстве программы Statistica v.8.0.Результаты. Обсуждаются алгоритм и результаты аналитического скрининга полиморфных вариантов 14 генов (PSMA1–PSMA7, PSMB1–PSMB7), кодирующих субъединицы 20S протеасомы. Даны характеристики панели SNР, составленной с учётом выбранных критериев отбора. По данным о частотах полиморфных вариантов генов анализируются особенности генофондов глобальных мировых и европейских популяций (283 SNP), а также выборок из популяций русских (20 SNP). По результатам анализа информации об ассоциациях отобранных SNP с различными заболеваниями сформирована панель (42 SNP) генов 20S протеасомы, потенциально значимых для исследования в качестве факторов-модификаторов баланса р105/р50 NFKB1.Заключение. Аннотирование сформированной панели SNP генов 20S протеасомы с MAF>0,1 свидетельствует о потенциальной роли полиморфизма в патогенезе заболеваний различного профиля. Это может представлять исследовательский интерес к сформированной панели в контексте реализации традиционных подходов – поиск генов-кандидатов на основе анализа ассоциаций с заболеваниями, а также анализа влияния SNP на уровень генетической экспрессии, синтез продуктов генов, процессинг NFKB1 и баланс р105/р50 in silico и на модельных объектах.

Aim. Formation of polymorphic variants panel of the proteasome genes 20S, potentially significant for the study as balance modifier factors of p105/p50 NFKB1.Materials and methods. Determination of genes that encode proteins of the multisubunit proteasome complex prospective for research purposes, was carried out on the basis of information retrieved from eLIBRARY and PubMed. The source of information for the formation of polymorphic variants panel of genes (SNP, single nucleotide polymorphism) was the Ensembl genomic browser, http://www.ensembl.org. The structure of genes is described by the NCBI (databases Gene, http:// www.ncbi.nlm.nih.gov/gene). The panel was filled with the minor allelic frequency in the population (MAF), the localization of SNP in the gene structure and the availability of data on the relationship with multifactorial diseases and other effects in mind. To calculate the genetic distances between populations, we used the methord of comparing the populations by frequencies of polymorphic marker alleles proposed by Ney, the obtained matrices are illustrated by the method of multidimensional scaling in space using Statistica v.8.0.Results. Discussion of the algorithm and results of analytical screening of polymorphic variants of 14 genes (PSMA1-PSMA7, PSMB1–PSMB7) encoding proteasome subunits 20S. The characteristics of the SNP panel are given, compiled with the selection criteria taken into account. According to the data on the frequencies of polymorphic gene variants, the features of global and European population gene pools (283 SNP), as well as samples from Russian populations (20 SNP) are analyzed. Based on the results of the analysis of information on the associations of selected SNPs with various diseases, a panel (42 SNPs) of 20S proteasome genes was formed, potentially significant for the study as factors modifying the p105/p50 NFKB1 balance.Conclusion. Annotation of the formed panel of SNP genes of the 20S proteasome with MAF>0.1 indicates the potential role of polymorphism in the pathogenesis of diseases of various profiles. This may be of research interest to the formed panel in context of implementation of traditional approaches – the search for candidate genes based on the analysis of associations with diseases, as well as the analysis of the influence of SNP on the level of genetic expression, synthesis of gene products, NFKB1 processing and p105/p50 balance in silico and on model objects.

NFKB1протеасома 20Sпроцессинггеныполиморфные вариантыNFKB1proteasome 20Sprocessinggenespolymorphic variantsРабота выполнена в рамках базового бюджетного источника финансирования работ государственного задания Минздрава РФ (Соглашение № 056-03-2023-050 от 17.01.2023. Авторы выражают искреннюю благодарность студентам лечебного факультета Кемеровского государственного медицинского университета Дутченко А.П., Шатобалову Я.И. за неоценимую помощь в подготовке рукописи статьи.The work was carried out within the framework of the basic budgetary source of financing the work of the state assignment of the Ministry of Health of the Russian Federation (Agreement No. 056-03-2023-050 dated 17.01.2023). The authors express their sincere gratitude to the students of the Medical Faculty of Kemerovo State Medical University A.P. Dutchenko, Ya.I. 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The authors declare that there are no conflicts of interest present.