# Comparative transcriptome analysis reveals genes associated with variation in liver copper concentration in Polish Merino sheep

## TL;DR

This study identifies genes linked to differences in liver copper levels in Polish Merino sheep, offering insights into managing copper-related health issues in sheep farming.

## Contribution

The study reveals novel candidate genes and pathways associated with liver copper concentration variation within a sheep breed.

## Key findings

- 53 genes were jointly identified as differentially expressed between high and low liver copper groups.
- Genes like MVD and DHCR7 were downregulated in high liver copper sheep and linked to cholesterol synthesis.
- Cholesterol biosynthesis and retinol metabolism pathways were enriched in the analysis.

## Abstract

Economic gain for sheep farmers is continually affected by incidences of copper intoxication and deficiency. This study assessed the ovine genome for differentially expressed genes (DEGs) influencing within-breed variation in hepatic copper content in Polish Merino sheep. To this end, we compared whole genome RNA sequence expression data from 12 female Polish Merino sheep liver samples (dataset 1) selected and grouped equally into high liver copper (HLC) and low liver copper (LLC) groups. Likewise, dataset 2 (a subset of dataset 1) containing 6 samples (HLC = 3; LLC = 3) was analyzed. The DEG analysis of HLC vs LLC groups for both data sets revealed a lower number of significant DEGs for dataset 1 (n = 64) when compared to dataset 2 (n = 252), respectively. Of the significant DEGs, 53 were jointly identified with both datasets. Identified DEGs downregulated in the HLC group including MVD, DHCR7, LOC101113583 and ERG28 are implicated in cholesterol synthesis, whereas AKR1B10 and CYP26A1 are associated with retinoic acid synthesis. The cholesterol biosynthetic process (GO:0006695) and the retinol metabolism (oas00830) were also observed by analysis of enriched gene ontologies, and Kyoto encyclopedia of genes and genomes pathways, respectively. Our findings provide new information on candidate genes associated with within-breed differences in hepatic copper concentration.

The online version contains supplementary material available at 10.1038/s41598-025-04330-8.