Identifying hepatic genes regulating the ovine response to gastrointestinal nematodes using RNA-Sequencing

Samantha Dixon; Niel A Karrow; Emma Borkowski; Aroa Suarez-Vega; Paula I Menzies; Delma Kennedy; Andrew S Peregrine; Bonnie A Mallard; Ángela Cánovas

doi:10.3389/fgene.2023.1111426

Identifying hepatic genes regulating the ovine response to gastrointestinal nematodes using RNA-Sequencing

Front Genet. 2023 Feb 17:14:1111426. doi: 10.3389/fgene.2023.1111426. eCollection 2023.

Authors

Samantha Dixon¹, Niel A Karrow¹, Emma Borkowski², Aroa Suarez-Vega¹, Paula I Menzies³, Delma Kennedy⁴, Andrew S Peregrine², Bonnie A Mallard², Ángela Cánovas¹

Affiliations

¹ Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada.
² Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
³ Department of Population Medicine, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
⁴ Ontario Ministry of Agriculture, Food and Rural Affairs, Guelph, ON, Canada.

Abstract

Gastrointestinal nematode (GIN) infections are considered the most important disease of grazing sheep and due to increasing anthelmintic resistance, chemical control alone is inadequate. Resistance to Gastrointestinal nematode infection is a heritable trait, and through natural selection many sheep breeds have higher resistance. Studying the transcriptome from GIN-exposed and GIN-unexposed sheep using RNA-Sequencing technology can provide measurements of transcript levels associated with the host response to Gastrointestinal nematode infection, and these transcripts may harbor genetic markers that can be used in selective breeding programs to enhance disease resistance. The objective of this study was to compare liver transcriptomes of sheep naturally exposed to Gastrointestinal nematode s, with either high or low parasite burdens, to GIN-unexposed control sheep in order to identify key regulator genes and biological processes associated with Gastrointestinal nematode infection. Differential gene expression analysis revealed no significant differentially expressed genes (DEG) between sheep with a high or low parasite burden (p-value ≤0.01; False Discovery Rate (FDR) ≤ 0.05; and Fold-Change (FC) of > ±2). However, when compared to the control group, low parasite burden sheep showed 146 differentially expressed genes (64 upregulated and 82 downregulated in the low parasite burden group relative to the control), and high parasite burden sheep showed 159 differentially expressed genes (57 upregulated and 102 downregulated in the low parasite burden group relative to the control) (p-value ≤0.01; FDR ≤0.05; and FC of > ±2). Among these two lists of significant differentially expressed genes, 86 differentially expressed genes (34 upregulated, 52 downregulated in the parasited group relative to the control) were found in common between the two parasite burden groups compared to the control (GIN-unexposed sheep). Functional analysis of these significant 86 differentially expressed genes found upregulated genes involved in immune response and downregulated genes involved in lipid metabolism. Results of this study offer insight into the liver transcriptome during natural Gastrointestinal nematode exposure that helps provide a better understanding of the key regulator genes involved in Gastrointestinal nematode infection in sheep.

Keywords: RNA sequenc ing; gastrointestinal nematode (GIN); liver; ovine; transcriptomics.

Grants and funding

The authors acknowledge financial support from the Ontario Ministry of Agriculture, Food, and Rural Affairs (OMAFRA, Ontario, Canada), the Ontario Agri-Food Innovation Alliance. The MSc scholarship for SD was funded by the OMAFRA Highly Qualified Personnel (HQP) Scholarship Program. This Project is a part of the Food from Thought research program at the University of Guelph, which is funded in part by the Canada First Research Excellence Fund.