An integrative systems biology approach to identify the molecular basis of sperm quality in swine

Abstract

Background:Genetic pressure in animal breeding is sparking the interest to select for elite boars with higher sperm quality to maximize ejaculate doses and fertility rates. However, the molecular basis of sperm quality remains largely unexplored. In this study, we sought to identify candidate genes, pathways and DNA variants associated to sperm quality in swine by analyzing 25 sperm-related phenotypes using a systems biology approach that integrates GWAS and RNA-seq.Results:By GWAS, we identified 12 QTL regions associated to the percentage of head and neck abnormalities, abnormal acrosomes and motile spermatozoa. Candidate genes included CHD2, KATNAL2, SLC14A2 or ABCA1. By RNA-seq, we detected 6,128 significant correlations between sperm traits and gene RNA abundances. We built a gene interaction network with the GWAS and the RNA-seq data. To build a robust gene interaction network, only the pair-wise interactions present in both the genetic co-association and the RNA co-abundance network were kept. Moreover, we also included to the Final Network both the genes which RNA abundances correlated with more than 4 semen traits as well as the miRNAs interacting with the genes on the network. The Final Network was enriched for genes involved in gamete generation and development, meiotic cell cycle, DNA repair or embryo implantation. We finally designed a panel of 73 SNPs provided from the GWAS, eGWAS and the Final Network, that explains between 5 to 36% of the phenotypic variance of the sperm traits.Conclusions:By means of a systems biology approach, we identified potential key genes affecting sperm quality. Furthermore, we propose a SNP panel that might explain a substantial part of the genetic variance for semen quality in swine and may thus be of interest for the pig breeding sector.