vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.451vavilov-1810Research ArticleМОЛЕКУЛЯРНЫЕ МАРКЕРЫ В ГЕНЕТИКЕ И СЕЛЕКЦИИBIOINFORMATICS AND SYSTEM BIOLOGYПриоритизация генов, ассоциированных с патогенезом лейкоза у крупного рогатого скотаPrioritization of genes associated with the pathogenesis of leukosis in cattleЮдинН. С.YudinN. S.yudin@bionet.nsc.ruПодколодныйН. Л.PodkolodnyyN. L.АгарковаТ. А.AgarkovaT. A.ИгнатьеваЕ. В.IgnatievaE. V.Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук4 Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics, SB RAS; Novosibirsk State UniversityRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук;; Институт вычислительной математики и математической геофизики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics, SB RAS; Institute of Computational Mathematics and Mathematical Geophysics, SB RASRussian FederationСибирский федеральный научный центр агробиотехнологий Российской академии наукРоссияSiberian Federal Research Center of Agro-BioTechnologies, RASRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics, SB RAS; Novosibirsk State UniversityRussian Federation20180201201922810631069Copyright © Юдин Н.С., Подколодный Н.Л., Агаркова Т.А., Игнатьева Е.В., 20192019Юдин Н.С., Подколодный Н.Л., Агаркова Т.А., Игнатьева Е.В.Yudin N.S., Podkolodnyy N.L., Agarkova T.A., Ignatieva E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1810

Перспективным подходом для искоренения инфекционных болезней сельскохозяйственных животных, особенно при отсутствии эффективных методов лечения и профилактики, считается направленная селекция по генетическим маркерам (однонуклеотидным полиморфизмам, минисателлитам). Вирус лейкоза крупного рогатого скота (ВЛКРС) распространен по всему миру и представляет одну из основных проблем для развития животноводства и продовольственной безопасности в России. Однако, как показали недавние полногеномные исследования, чувствительность/резистентность к инфекции ВЛКРС носит полигенный характер. Целью исследования было создание каталога генов крупного рогатого скота и других видов млекопитающих, вовлеченных в процесс патогенеза инфекции ВЛКРС, и приоритизация генов каталога с помощью методов биоинформатики. Путем ручного сбора информации из открытых источников нами создан каталог генов крупного рогатого скота и других видов млекопитающих, вовлеченных в процесс патогенеза инфекции ВЛКРС, включающий 446 генов. Приоритизацию генов каталога осуществляли на основе следующих критериев: 1) ген ассоциирован с лейкозом по данным полногеномного анализа ассоциаций; 2) ген ассоциирован с лейкозом по данным анализа ассоциаций «случай–контроль»; 3) роль гена в развитии лейкоза изучена в экспериментах по нокауту у мышей; 4) белок, кодируемый геном, участвует в белок-белковых взаимодействиях с вирусной частицей либо отдельным вирусным белком; 5) ген имеет аннотацию терминами Gene Ontology, которые являются перепредставленными для данного списка генов; 6) ген участвует в биологических путях из баз KEGG или REACTOME, которые являются перепредставленными для данного списка генов; 7) белок, кодируемый геном, имеет неслучайно высокое количество белокбелковых взаимодействий с белками, кодируемыми другими генами из каталога. На основе каждого критерия гену присваивали ранг. Затем ранги суммировали и определяли общий ранг. Приоритизация списка, включающего 446 генов, позволила выделить пять наиболее вероятных генов-кандидатов (TNF, LTB, BOLA-DQA1, BOLA-DRB3, ATF2), которые могут влиять на чувствительность/устойчивость крупного рогатого скота к заболеванию лейкозом.

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF, LTB, BOLA-DQA1, BOLA-DRB3, ATF2), which can affect the sensitivity/resistance of cattle to leukemia.

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