Expression Quantitative Trait Loci and Allele-Specific Expression Exhibiting Joint Association with Polygenic Trait Phenotypes in Pigs

摘要

Significant genetic gain in pork production has been achieved in the past 30 years. Advancements in sequencing technology, improvements in the annotation of the pig genome, and development of quantitative genetic models were instrumental in the these efforts. Several quantitative trait locus (QTL) have been identified for growth, meat quality and carcass composition phenotypes, however, the biological mechanisms underlying most QTL remain unknown. Functional genomic analysis can reveal insights on the genetic architecture of complex traits, and transcriptomic profiling of skeletal muscle during the initial steps leading to the conversion of muscle to meat can identify key regulators of meat quality and carcass phenotypes. In this study, we aimed to identify potential candidate genes and molecular markers regulating phenotypic traits using an F2 Duroc x Pietrain pig resource population. Gene transcripts obtained with RNA-seq of longissimus dorsi muscle from 168 F2 animals were used to estimate gene expression variation subject to genetic control by mapping expression QTL (eQTL), and identifying allele-specific expression (ASE). A total of 334 eQTL were mapped (FDR ≤ 0.01) with 187 exhibiting local acting regulation. Joint association of eQTL with phenotypic QTL (pQTL) segregating in our population revealed 16 genes significantly associated with 21 pQTL for meat quality, carcass composition and growth traits. Ten of these pQTL were for meat quality phenotypes that co-localized with one eQTL on SSC2 (8.8Mb region) and a putative hotspot associated with 11 gene transcripts on SSC15 (121Mb region). Biological processes identified for co-localized eQTL genes associated with meat quality traits included calcium signaling (MRLN, PKP2 and CHRNA9), energy metabolism (SUCLG2 and PFKFB3) and redox hemostasis (NQO1 and CEP128).;Allele specific expression (ASE) analysis facilitates the identification of cis-acting regulation of transcript abundance, which can be associated with a measurable phenotypic difference. In this study, we tested for ASE in 69,502 coding SNP (cSNP) called directly from longissimus dorsi transcriptomes. A total of 18,234 cSNP with significant ASE were identified (FDR ≤ 0.01). A meta-analysis merging cSNP p-values per gene identified 4,170 genes with significant allele-specific effects (FDR ≤ 0.01). A gene-wise conditional analysis fitting all ASE cSNP per gene for each phenotype identified 60 genes associated with growth, carcass composition and meat quality phenotypes. Ring finger and Zinc finger transcription factors were associated with 45-min pH, drip loss and 10th-rib backfat, and allelic expression bias for these genes was confirmed with pyrosequencing. Six genes exhibiting significant cis-acting effects and two genes associated with both cis and trans action were key regulators of the PI3K-Akt-mTOR signaling pathway. PI3K-Akt-mTOR plays an important role in skeletal muscle response to acute hypoxia, regulates cellular hypertrophy, and has been implicated in glycolytic metabolism. Results support an important role for activation of the PI3K-Akt-mTOR signaling pathway during the initial conversion of muscle to meat.