Pleiotropic architectures of porcine immune and growth trait pairs revealed by a self-product-based transcriptome method.

Abstract

Pleiotropy is an important biological phenomenon with complicated genetic architectures for multiple traits. To date, pleiotropy has been mainly identified by multi-trait genome-wide association studies, but this method has its disadvantages, and new developments for pleiotropy detection methods are needed. Here we define a novel metric, self-product, to measure individual-level co-variation of two traits, and develop a novel self-product-based transcriptome method to detect pleiotropic genes (PGs). Our method was tested using four immune-growth trait pairs and four immune-immune trait pairs in pigs. Comparative transcriptome analyses identified hundreds of candidate PGs related to eight trait pairs from two tails of self-product distribution. Gene Ontology enrichment analysis indicated that most of identified PGs were involved in immune- or growth-related biological processes. We established PG interaction networks to exhibit core genes shared by eight trait pairs, of which CCL5 and IL-10 genes were the hub genes. Genetic association analyses showed that SmaI-polymorphisms of CCL5 and IL-10 genes had significant associations with phenotypic co-variations of multiple trait pairs, indicating that the variants in pleiotropic genes were also pleiotropic variants. Taken together, the validity of our proposed method was preliminarily verified, and our findings provide new insights into the genetic basis of pleiotropic architectures of immune and growth trait pairs in pigs.