Abstract
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.
Highlights
Перспективным подходом для искоренения инфекционных болезней сельскохозяйственных животных, особенно при отсутствии эффективных методов лечения и профилактики, считается направ ленная селекция по генетическим маркерам
Recent genome-wide association studies have shown that sensitivity/resistance to Bovine leukemia virus (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
Summary
Приоритизация генов, ассоциированных с патогенезом лейкоза у крупного рогатого скота. Вирус лейкоза крупного рога того скота (ВЛКРС) распространен по всему миру и п редставляет одну из основных проблем для развития животноводства и продо вольственной безопасности в России. Целью иссле дования было создание каталога генов крупного рогатого скота и других видов млекопитающих, вовлеченных в процесс патогенеза инфекции ВЛКРС, и приоритизация генов каталога с помощью ме тодов биоинформатики. Путем ручного сбора информации из открытых источников нами создан каталог генов крупного рогатого скота и других видов млекопитающих, вовлеченных в процесс па тогенеза инфекции ВЛКРС, включающий 446 генов. Прио ритизация списка, включающего 446 генов, позволила выделить пять наиболее вероятных генов-кандидатов (TNF, LTB, BOLA-DQA1, BOLA-DRB3, ATF2), которые могут влиять на чувствительность/ус тойчивость крупного рогатого скота к заболеванию лейкозом. Ключевые слова: вирус лейкоза крупного рогатого скота; полногеномный анализ ассациаций; ген; однонуклеотидный полиморфизм; ассоциация; приоритизация; GO анализ; белокбелковое взаимодействие
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