GWAS analyses reveal MHC genes associated with a reproductive trait in Nellore cattle

Understanding which pathways are involved in the phenotypic expression of complex traits could reveal key genes affecting the trait of interest. The aim of this study was to identify important pathways associated with the number of calves at 53 months of age (NC53) in Nelore cows. The data contained 244,311 cows, of which, 38%, 28.6% and 33.4% had 0, 1 or 2 calving, respectively. There were 369,878 animals in the pedigree distributed over 5 generations. After quality control remained 409,376 SNPs and 2,923 samples. The SNP effects were estimated by the weighted single-step GBLUP (Wang et al., 2012). Predicted breeding values were obtained using the threshold animal model (Gianola & Foulley, 1983): , where y is a vector of underlying liabilities for NC53, ? is a vector of fixed effects of contemporary group (herd, year, season and management group), a is a vector of random additive direct genetic effects (breeding values), X and Z_a are incidence matrices relating elements in ? and a to y, respectively, and e is the vector of residuals. Cytoscape and DAVID softwares were used to determine significant pathways. Asthma was the group presenting the higher significance level (p-value = 1.1E^-9) in Cytoscape analysis. The top Go term from DAVID analysis (ES = 7.8) was the Major Histocompatibility Complex (MHC) class II protein. The MHC genes, BLA-DQB, BOLA-DQA1, BOLA-DQA2, BOLA-DQB, BOLA-DRA and HLA-DQA1 were identified in both analyses, and are located in BTA23, window 26Mb. The MHC role is to recognize the compatibility between tissues, as in allograft case, consequently is associated with immune response. MHC is composed by a highly polymorphic gene group, its variability is desired by the ability of the immune system to recognize and fight pathogens (Nicholas, 1996). Also, males and females choose their sexual partner based on dissimilar MHC (Ziegler et al., 2010). However, with artificial selection and mating systems, animals are limited to choose their partners, especially when artificial insemination is used, what is speculated to impose a barrier to the pregnancy success. The MHC genes are candidates to affect NC53, suggesting the immune system is controlling the pregnancy success in Nelore cows, as already confirmed in other breeds and species.