Abstract
MicroRNAs (miRNA) are key modulators of gene expression and so act as putative fine-tuners of complex phenotypes. Here, we hypothesized that causal variants of complex traits are enriched in miRNAs and miRNA-target networks. First, we conducted a genome-wide association study (GWAS) for seven functional and milk production traits using imputed sequence variants (13~15 million) and >10,000 animals from three dairy cattle breeds, i.e., Holstein (HOL), Nordic red cattle (RDC) and Jersey (JER). Second, we analyzed for enrichments of association signals in miRNAs and their miRNA-target networks. Our results demonstrated that genomic regions harboring miRNA genes were significantly (P < 0.05) enriched with GWAS signals for milk production traits and mastitis, and that enrichments within miRNA-target gene networks were significantly higher than in random gene-sets for the majority of traits. Furthermore, most between-trait and across-breed correlations of enrichments with miRNA-target networks were significantly greater than with random gene-sets, suggesting pleiotropic effects of miRNAs. Intriguingly, genes that were differentially expressed in response to mammary gland infections were significantly enriched in the miRNA-target networks associated with mastitis. All these findings were consistent across three breeds. Collectively, our observations demonstrate the importance of miRNAs and their targets for the expression of complex traits.
Highlights
Understanding the genetic architecture, i.e., knowledge of causal genomic variants, their allele frequencies and effect sizes, underpinning complex phenotypes and diseases is a long ongoing quest in the field of genetics and genomics[1,2,3]
Genomic sequence variation can affect miRNAs functions in several ways: Variants can occur in sequences that are responsible for driving the expression of miRNA genes; variants can disrupt or create miRNA binding sites in target mRNAs; and the miRNAs themselves can exist as variants[35]
Infection-induced transcriptome data were integrated to validate the significant miRNA-target networks detected for mastitis, and to investigate the underlying genetic and biological basis of our findings
Summary
Understanding the genetic architecture, i.e., knowledge of causal genomic variants, their allele frequencies and effect sizes, underpinning complex phenotypes and diseases is a long ongoing quest in the field of genetics and genomics[1,2,3]. By integrating genome functional annotations with GWAS data, Finucane et al (2015) revealed conserved genomic regions that were strongly enriched with genetic variation of many complex traits in human[25]. Computational estimates suggest that more than 30% of all protein-coding genes in human are regulated by miRNAs31–34 This strongly indicates that miRNAs have widespread roles in vivo, and that all genetic networks and pathways are expected to be regulated to some degree by miRNAs. Genomic sequence variation can affect miRNAs functions in several ways: Variants can occur in sequences that are responsible for driving the expression of miRNA genes; variants can disrupt or create miRNA binding sites in target mRNAs; and the miRNAs themselves can exist as variants[35]. We aimed to investigate the joint effect of genetic variations in miRNA genes and in their targets-networks on complex traits of economic importance in dairy cattle
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
