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

CARIGNANO HUGO; ROLDAN DI BERBIE JOSE MARIA; RASCHIA MARIA; AMADIO ARIEL FERNANDO; NANI JUAN; GERONIMO GUTIERREZ; ALVAREZ IRENE; TRONO KARINA; POLI MARIO; MIRETTI MARCOS

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

carignano Hugo, Roldan Di Baribie Maria Jose, Raschia Maria, Amadio Ariel Fernando, Naani Juan, Gutierrez Geronimo, Alvarez Irene, Trono Karina, Poli Mario, Miretti MarcosBovine Leukemia Virus Genetic Association Study Reveals Novel Host Genes Probably Influencing White Blood Cells Counts in Naturally Infected Dairy CattleBovine Leukemia Virus (BLV) infection is ubiquitous in dairy cattle provoking important an important economic impact because of lymphosarcoma-related deaths, trade restrictions and increased culling rate at herd level. The BLV provirus persists throughout the life span of infected cows and an inter-individual variation is observed in the level of infection (LI) in vivo. High LI is strongly correlated with disease progression and BLV dissemination to healthy herdmates. The high endimicity and the economically impractical implementation of classical BLV control strategies make BLV suitable for host genomics studies aiming to dissect loci associated with LI, potentially useful for genetic selection programs tending to limit the viral spreading. The LI was measured through the proviral load (PVL) set?point and White Blood Cells (WBC) counts in Holstein and Jersey crosses cows. The goals of this work were gain insight into the contribution of SNPs (bovine 50KSNP panel) on BLV LI variability and identify candidates genomics regions underlined this trait.We determined the antibody response (anti?p24) and total leukocytes in peripheral blood of 1800 cows and used it to select 800 individuals with extreme phenotypes in WBCs and PVL. Two case-control genomic association studies using LMMs considering population stratification were performed. The genetic variance captured by QC-passed SNPs represented 0.63 ± 0.14 of the phenotypic variance for PVL and 0.56 ± 0.15 for WBCs. Overall, significant associations (Bonferroni´s corrected -log10(p) > 5.94) were shared for both phenotypes in 24 SNPs within the Bovine MHC. Founder haplotypes were used to calculate the LD decay (r2 = 0.22 ± 0.27 at inter-SNP distance of 2550 kb) to assign gene annotation to GWAS hits. The SNPs and LD blocks indicated genes potentially associated with LI in infected cows: i.e. relevant immune response related genes (DQA1, DRB3, BOLA-A, LTA, LTB, TNF, IER3, GRP111, CRISP1), several genes