Bovine Leukemia Virus Genetic Association Study Reveals Novel Host Genes Probably Influencing White Blood Cells Counts in Naturally Infected Dairy Cattle.

CARIGNANO HUGO ; RASCHIA MARIA; GERÓNIMO GUTIÉRREZ; POLI MARIO; ROLDAN D; ARIEL FERNANDO AMADIO; ALVAREZ IRENE; MIRETTI MARCOS; BERIBIE MARIA JOSE; JUAN NANI; KARINA TRONO

TOKYO

Workshop; 18th International Conference on Human Retrovirology: HTLV and Related Viruses; 2017

Bovine Leukemia Virus Genetic Association Study Reveals Novel HostGenes Probably Influencing White Blood Cells Counts in NaturallyInfected Dairy Cattle.Hugo A. Carignano1, Dana L. Roldan1, María J. Beribe2, María A. Raschia1, Ariel Amadio3,4,Juan P. Nani3, Gerónimo Gutierrez5, Irene Alvarez5,4, Karina Trono5, Mario A. Poli1 andMarcos M. Miretti6,4.1Instituto de Genética, CICVyA ? INTA, Hurlingham B1686, Argentina.2EEA Pergamino ? INTA, Pergamino B2700, Argentina. 3EEA Rafaela ? INTA, Rafaela S2300, Santa Fe, Argentina.4CONICET, Ciudad Autónoma de Buenos Aires C1033AAJ, Argentina.5Instituto de Virología, CICVyA ? INTA, Hurlingham B1686, Argentina.6Grupo de Investigación en Genética Aplicada, Instituto de Biología Subtropical (GIGA- IBS) UNaM-CONICET, Posadas N3300, Argentina.Background Bovine Leukemia Virus (BLV) infection is ubiquitous in dairy cattle causingimportant economic losses because of lymphosarcoma-related deaths, trade restrictions andincreased culling rate at herd level. Among infected animals a substantial variation isobserved in the White Blood Cells (WBC) counts. The development of high WBC counts isconsidered as a key factor for the horizontal and vertical BLV transmission. The highendimicity, variability in the host´s immune response and the economically unfeasibleimplementation of classical BLV control strategies, strengthen the search for host genomicsloci associated with this trait, potentially useful for genetic selection programs to limit theviral spreading. In this work we aimed to gain insight into the host immune response factorscontributing to BLV infection dynamics and to identify genomics regions potentially involvedin BLV infection spreading.Methods We determined the anti-p24 response and total leukocytes in peripheral blood of1800 cows and used it to select individuals with extreme phenotypes in WBCs. A case-control genome-wide association study using mixed models considering populationstratification was performed.Results After Bonferroni´s multiple testing correction, 11 SNPs were significantly associated(p > 1.15 x 10-6) with WBC counts level. All of them mapping within the Bovine MHC. Theassignation of genes to SNPs utilizing the linkage disequilibrium extent identified genespotentially associated with WBCs levels in infected cows: i.e. immune response related genes(DQA1, TRIM31, TRIM40, IER3, GRP111, CRISP1), an apoptotic regulator gene (BAG6) andseveral host transcription factors (TFAP2D, GCM-1, ABT1).Conclusion Data obtained are relevant to understand the pathobiology of BLV?bovineinterplay, and provide useful genomic information applicable to selective breeding programs