Paternal genetic background orchestrates fetal development through tissue-specific cis-regulatory divergence
Muhammad Arsalan Iqbal1, Eduard Murani1, Frieder Hadlich1
1Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Iscience
|July 28, 2026
Summary
Paternal genetics significantly impacts fetal development by altering gene expression across tissues. This study reveals how sire breed influences fetal transcription and regulatory landscapes, offering insights into livestock trait improvement.
Area of Science:
- Genomics
- Developmental Biology
- Animal Science
Background:
- Paternal genetic effects on offspring development extend beyond basic inheritance.
- Understanding how sire genetics influences fetal transcription and regulatory landscapes across tissues is crucial.
Purpose of the Study:
- To investigate the impact of paternal breed on fetal transcriptional and cis-regulatory landscapes in pigs.
- To identify specific genes and regulatory mechanisms mediating sire-breed effects on fetal development.
Main Methods:
- Utilized a reciprocal backcross pig model (F1 × German Landrace vs. F1 × Piétrain).
- Employed a haplotype-agnostic RNA-sequencing pipeline to profile six fetal tissues.
- Conducted allele-specific expression (ASE) analysis to assess cis-regulatory divergence.
Main Results:
- Identified 1,176 differentially expressed genes driven by paternal breed, with pronounced effects in metabolic tissues.
- Observed tissue-specific transcriptional trade-offs: German Landrace favored metabolic pathways, Piétrain upregulated developmental processes.
- Revealed extensive, tissue-dependent cis-regulatory divergence, highlighting candidate genes like SLC5A12, IVD, BRD3, and CES1.
Conclusions:
- Paternal genetics programs fetal tissues through cis-regulatory variation, impacting offspring development.
- Findings suggest that regulatory variants link sire background to performance phenotypes and fetal programming.
- This research provides a foundation for improving livestock traits through understanding paternal genetic influences.
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