A multi-tissue atlas of allelic-specific expression reveals the characteristics, mechanisms, and relationship with dominant effects in cattle.

Abstract

Background: Allele-specific expression (ASE) analysis is a crucial tool for validating expression quantitative trait loci (eQTLs), identifying causal variants associated with complex traits, and investigating the genetic mechanisms underlying heterosis. In this study, we characterized ASE variants across 35 tissues using 7532 publicly available RNA-seq datasets. Additionally, we explored the mechanisms driving ASE through integration with epigenomic data and examined the relationship between ASE and dominance effects on gene expression and milk-related traits in Holstein cattle.

Results: ASE variants exhibited stronger tissue specificity and lower reproducibility compared to eQTLs. Interestingly, variants with opposite directional effects demonstrated greater resilience across diverse environments. Functional annotation revealed that ASE variants were enriched in both enhancer and promoter regions during transcription and implicated in post-transcriptional and translational processes, including mutations that affect mRNA splicing and trigger nonsense-mediated decay. Analysis of eQTLs, splicing QTLs (sQTLs), and validated QTLs associated with milk-related traits in Holstein cattle, coupled with enrichment analysis in QTL databases and effect size evaluation, indicated that ASE variants were more closely aligned with dominant effects than additive effects, particularly in reproductive and immune-related tissues/traits, which exhibited higher levels of heterosis.

Conclusions: Our findings not only enhance our understanding of the genetic mechanisms underlying heterosis and ASE formation but also provide a valuable resource of regulatory variants that can be leveraged to improve economic traits through molecular breeding or the strategic exploitation of heterosis.