PSX-1 - Genomic insights into reproduction traits of Nellore cattle: A meta-analysis of genomic regions

Abstract: Enhancing reproductive efficiency could lead to economic benefits for Nellore producers. However, several factors limit our understanding of the main genetic factors controlling reproduction traits in Nellore cattle, including genetic differences between populations and statistical limitations. A meta-analysis can assist in pinpointing the most likely functional candidate genes, quantitative trait loci, and biological processes simultaneously associated with several traits in a group. Hence, the goal of this study was to perform a meta-analysis of genomic regions previously associated with reproduction traits in Nellore cattle, in order to improve our comprehension of the main genetic mechanisms regulating these traits within the breed. This study incorporated a total of 549 genomic regions sourced from 21 scientific publications, published between 2014 to 2024. The reproduction traits included in this study are scrotal circumference at various ages (365, 450, and 550 days), early pregnancy (< 31 months of age), early puberty (defined as pregnancy at 18 months), age at first calving, antral follicle count, calving interval, calving ease, testicular hypoplasia, stayability, heifer rebreeding, gestation length, anti-mullerian hormone levels, preweaning calf mortality, and post-natal mortality. All genomic regions identified in the literature were updated to the ARS-UCD1.2 genome assembly, and the Gallo R package was used to identify positional candidate genes associated with each genomic region. A total of 8,441 positional candidate genes were annotated and used in an overrepresentation analysis performed in meshr. The significant genes (adjusted p-values< 0.05) identified in the overrepresentation analysis underwent prioritization analyses using the GUILDify and ToppGene software. Subsequently, enrichment analysis of the prioritized overrepresented candidate genes was performed using the ClusterProfiler R package. The 8,441 annotated genes generated 1,757 overrepresented genes, of which 17 candidate genes were prioritized (FDR p-value≤10^-3). The overrepresented candidate genes that were prioritized are: SERTAD2, RFWD3, C1QTNF9B, SLFN14, CATSPERE, GFRA4, ZNF408, NOP58, ADGRG3, KIZ, REM2, FSCN3, DCAF11, ACSM4, ANKRD34B, CMKLR2-AS, and TRV-AAC1-1. The functional enrichment analysis highlighted the following genes: FSCN3 (exhibits highly specific expression in testis), CATSPERE (plays a vital role in cellular processes related to reproduction and is necessary for normal fertility), ANKRD34B (associated with cytoplasm found in oocytes or early embryos), and RFWD3 (regulates the transition between phases of the mitotic cell cycle). All other prioritized genes also play roles in regulating metabolic pathways or biological processes related to reproduction, such as sperm capacitation, sperm motility, cilium or flagellum-dependent cell motility, mitotic cell cycle phase transition, and RNA endonuclease activity. The enrichment of the functional candidate genes identified highlights that these genes play an important role in the expression of reproduction traits in Nellore cattle. Candidate genes identified in this study can be used as target genes in gene expression studies, which are necessary to validate our findings.