Multi-Tissue Omics Analysis Uncovers Translational Regulation Underlying Complex Traits in Pigs

Area of Science:

• Genomics
• Molecular Biology
• Quantitative Genetics

Background:

• Genetic variations influencing gene transcription and translation are crucial for complex traits and diseases.
• Systematic analysis of variants regulating both transcription and translation, and their role in complex trait genetics, is limited.

Purpose of the Study:

• To develop a novel framework for prioritizing gene regulatory networks (GRNs) underlying complex traits by integrating multi-omics data.
• To identify genetic variants that regulate gene translation and contribute to phenotypic variation.

Main Methods:

• Generated a multi-omics dataset (transcriptomic, translational, proteomic, whole-genome sequencing) across 16 tissues and two pig breeds.
• Employed integrative analysis of transcriptional and translational profiles, population genetics, and dual-luciferase reporter assays.
• Utilized RNA interference assays to confirm gene functions.

Main Results:

• Demonstrated widespread translational buffering/amplification and significant contribution of translation efficiency (TE) to phenotypic variation.
• Identified 33 functional 5'UTR variants associated with pork production traits by modulating TE in 14 target genes.
• Confirmed the involvement of AQP4 and MYO18B in myogenic differentiation, with specific variants affecting TE through RNA structure or protein interactions.

Conclusions:

• The developed framework effectively prioritizes GRNs and identifies functional variants impacting complex traits through translational regulation.
• This approach extends beyond traditional transcriptional regulation for uncovering the genetic basis of complex traits.
• Identified specific variants in AQP4 and MYO18B that influence TE and are relevant to muscle development.