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Summary
This summary is machine-generated.

Genetic variations in gene translation significantly impact complex traits. This study introduces a new framework to identify variants affecting translation efficiency (TE), revealing 33 functional variants linked to pork production traits.

Keywords:
gene regulatory networkpigpost‐transcriptional regulationtranslationvariants

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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.