vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-34vavilov-3739Research ArticleБИОИНФОРМАТИКАBIOINFORMATICSКомпиляция и функциональная классификация генов, ассоциированных с длиной теломер, у человека и других видов животныхCompilation and functional classification of telomere length-associated genes in humans and other animal specieshttps://orcid.org/0000-0002-8588-6511ИгнатьеваЕ. В.IgnatievaE. V.

Новосибирск

Novosibirsk

eignat@bionet.nsc.ruhttps://orcid.org/0000-0002-1947-5554ЮдинН. С.YudinN. S.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-7859-6201ЛаркинД. М.LarkinD. M.

Новосибирск

Novosibirsk

dmlarkin@gmail.comФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian Federation202302062023273283292Copyright © Игнатьева Е.В., Юдин Н.С., Ларкин Д.М., 20232023Игнатьева Е.В., Юдин Н.С., Ларкин Д.М.Ignatieva E.V., Yudin N.S., Larkin D.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3739

Теломеры – это концевые участки хромосом, обеспечивающие их стабильность в ходе клеточного деления. Укорочение теломер инициирует процесс старения клеток, что может приводить к дегенерации и атрофии тканей. Укорочение теломер связано с сокращением продолжительности жизни и с предрасположенностью к ряду заболеваний, поэтому данный показатель может быть использован в качестве предиктора продолжительности жизни и состояния здоровья отдельного индивида. Длина теломер – сложный фенотипический признак, который определяется многими факторами, в том числе генетическими. Многочисленные исследования (включая полногеномный анализ ассоциаций, ПГАА) свидетельствуют о полигенном характере контроля длины теломер. Цель работы – охарактеризовать генетические основы регуляции длины теломер на основе данных ПГАА, полученных при исследовании различных популяционных выборок человека и других животных. Для этого авторами была собрана компиляция генов, ассоциированных с длиной теломер по данным ПГАА, которая включала сведения о 270 генах человека, а также 23, 22 и 9 генах, выявленных у крупного рогатого скота, домового воробья и нематоды соответственно. Среди них присутствовали два гена-ортолога, кодирующих белок шелтеринового комплекса (POT1 у человека и pot-2 у C. elegans). Функциональный анализ показал, что на длину теломер могут влиять генетические варианты в генах, кодирующих: 1) структурные компоненты теломеразы; 2) белковые компоненты теломерных участков хромосом (шелтериновый комплекс и CST комплекс); 3) белки, участвующие в биогенезе теломеразы и регулирующие ее активность; 4) белки, регулирующие функциональную активность компонентов шелтеринового комплекса; 5) белки, участвующие в репликации и/или кэпировании теломер; 6) белки, контролирующие альтернативный путь удлинения теломер;

7) белки, реагирующие на повреждения ДНК и отвечающие за репарацию; 8) компоненты РНК экзосом. В работе выявлены гены человека, идентифицированные несколькими исследовательскими группами в популяциях различного этнического происхождения. Это гены, кодирующие компоненты теломеразы (TERC и TERT), а также ген STN1, кодирующий белок CST комплекса. По-видимому, полиморфные локусы, затрагивающие функции этих генов, могут быть наиболее надежными маркерами предрасположенности к заболеваниям, связанным с длиной теломер. Систематизированные нами данные о генах и их функциях будут полезны при разработке прогностических критериев заболеваний человека, для которых показана связь с длиной теломер. Сведения о генах и процессах, контролирующих длину теломер, могут быть востребованы для маркер-ориентированной и геномной селекции сельскохозяйственных животных, направленной на повышение продолжительности их хозяйственного использования.

Telomeres are the terminal regions of chromosomes that ensure their stability while cell division. Telomere shortening initiates cellular senescence, which can lead to degeneration and atrophy of tissues, so the process is associated with a reduction in life expectancy and predisposition to a number of diseases. An accelerated rate of telomere attrition can serve as a predictor of life expectancy and health status of an individual. Telomere length is a complex phenotypic trait that is determined by many factors, including the genetic ones. Numerous studies (including genome-wide association studies, GWAS) indicate the polygenic nature of telomere length control. The objective of the present study was to characterize the genetic basis of the telomere length regulation using the GWAS data obtained during the studies of various human and other animal populations. To do so, a compilation of the genes associated with telomere length in GWAS experiments was collected, which included information on 270 human genes, as well as 23, 22, and 9 genes identified in the cattle, sparrow, and nematode, respectively. Among them were two orthologous genes encoding a shelterin protein (POT1 in humans and pot-2 in C. elegans). Functional analysis has shown that telomere length can be influenced by genetic variants in the genes encoding: (1) structural components of telomerase; (2) the protein components of telomeric regions (shelterin and CST complexes); (3) the proteins involved in telomerase biogenesis and regulating its activity; (4) the proteins that regulate the functional activity of the shelterin components; (5) the proteins involved in telomere replication and/or capping; (6) the proteins involved in the alternative telomere lengthening; (7) the proteins that respond to DNA damage and are responsible for DNA repair; (8) RNA-exosome components. The human genes identified by several research groups in populations of different ethnic origins are the genes encoding telomerase components such as TERC and TERT as well as STN1 encoding the CST complex component. Apparently, the polymorphic loci affecting the functions of these genes may be the most reliable susceptibility markers for telomere-related diseases. The systematized data about the genes and their functions can serve as a basis for the development of prognostic criteria for telomere length-associated diseases in humans. Information about the genes and processes that control telomere length can be used for marker-assisted and genomic selection in the farm animals, aimed at increasing the duration of their productive lifetime.

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