TY - JOUR

T1 - Prioritization of genes associated with the pathogenesis of leukosis in cattle

AU - Yudin, N. S.

AU - Podkolodnyy, N. L.

AU - Agarkova, T. A.

AU - Ignatieva, E. V.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Association

KW - Bovine leukemia virus

KW - Gene

KW - Genome-wide association study

KW - GO analysis

KW - Prioritization

KW - Protein-protein interactions

KW - Single-nucleotide polymorphism

KW - bovine leukemia virus

KW - genome-wide association study

KW - gene

KW - single-nucleotide polymorphism

KW - association

KW - prioritization

KW - GO analysis

KW - protein-protein interactions

KW - BOVINE LEUKEMIA-VIRUS

KW - GENOME-WIDE ASSOCIATION

KW - BETA

KW - HOLSTEIN

KW - IDENTIFICATION

KW - POLYMORPHISMS

KW - PROGRESSION

UR - http://www.scopus.com/inward/record.url?scp=85064805957&partnerID=8YFLogxK

U2 - 10.18699/VJ18.451

DO - 10.18699/VJ18.451

M3 - Article

AN - SCOPUS:85064805957

VL - 22

SP - 1063

EP - 1069

JO - Вавиловский журнал генетики и селекции

JF - Вавиловский журнал генетики и селекции

SN - 2500-0462

IS - 8

ER -