Identification and functional annotation of candidate genes and transcription factors associated with reproductive traits to Nelore bulls: new insights from GWAS and post-GWAS analysis.

Reproductive traits of cattle, especially the Nelore breed, have notable importance in the global economy and are recognized throughout the beef cattle production system. Therefore, we aimed to identify regulatory networks of transcription factors (TFs) and the most promising candidate genes for scrotal circumference (SC), testicular hypoplasia (HT), and sexual precocity (SP) that were previously identified in GWAS analysis. We identified 444 genes from a peer-reviewed systematic review related to male reproductive traits. Biological processes were then identified using DAVID 6.8, and a regulatory network of TFs was constructed. Enriched biological processes and seven candidate genes (BICC1, CDH1, FOXG1, GHR, OR52E4, SLC17A7, and ITGA2) were identified, which were associated with some biological processes linked to reproduction. Furthermore, gene-TF networks were obtained from TFs (GABPA, HNF1A, HNF4A, PAX2, and TFAP2A) associated with bovine reproduction, and the 22 most promising candidate genes (CDKN2C, CLPTM1L, GCSAM, GPR12, GTF3A, HSPBAP1, IL32, ILDR1, LOC100141258, LOC100336282, LOC107131530, LOC112449111, LOC618541, LOC781785, MIX23, MTIF3, PARP9, PCED1B, RNASE2, SLC39A2, SPA17 and TMEM253) were found to be specifically linked to sexual precocity. The identified candidate genes and transcription factors have significant potential to influence the evaluated traits in Nelore bulls. Future research and applications of these genetic factors may improve the breeding and enhancement of Nelore cattle.