Genomic regions and biological pathways associated with sex-limited reproductive traits in bovine species

Many animal species exhibit sex-limited traits, where certain phenotypes are exclusively expressed in one sex. Yet, the genomic regions that contribute to these sex-limited traits in males and females remain a subject of debate. Reproductive traits are ideal phenotypes to study sexual differences since they are mostly expressed in a sex-limited way. Therefore, this study aims to use local correlation analyses to identify genomic regions and biological pathways significantly associated with male and female sex-limited traits in two distinct cattle breeds (Brahman [BB] and Tropical Composite [TC]). We used the Correlation Scan method to perform local correlation analysis on 42 trait pairs consisting of six female and seven male reproductive traits recorded on similar to 1,000 animals for each sex in each breed. To pinpoint a specific region associated with these sex-limited reproductive traits, we investigated the genomic region(s) consistently identified as significant across the 42 trait pairs in each breed. The genes found in the identified regions were subjected to Quantitative Trait Loci (QTL) colocalization, QTL enrichment analyses, and functional analyses to gain biological insight into sexual differences. We found that the genomic regions associated with the sex-limited reproductive phenotypes are widely distributed across all the chromosomes. However, no single region across the genome was associated with all the 42 reproductive trait pairs in the two breeds. Nevertheless, we found a region on the X-chromosome to be most significant for 80% to 90% (BB: 33 and TC: 38) of the total 42 trait pairs. A considerable number of the genes in this region were regulatory genes. By considering only genomic regions that were significant for at least 50% of the 42 trait pairs, we observed more regions spread across the autosomes and the X-chromosome. All genomic regions identified were highly enriched for trait-specific QTL linked to sex-limited traits (percentage of normal sperm, metabolic weight, average daily gain, carcass weight, age at puberty, etc.). The gene list created from these identified regions was enriched for biological pathways that contribute to the observed differences between sexes. Our results demonstrate that genomic regions associated with male and female sex-limited reproductive traits are distributed across the genome. Yet, chromosome X seems to exert a relatively larger effect on the phenotypic variation observed between the sexes.