Variants within genes EDIL3 and ADGRB3 are associated with divergent fecal egg counts in Katahdin sheep at weaning

Authors: BECKER, GABRIELLE - UNIVERSITY OF IDAHO; Burke, Joan; LEWIS, RON - UNIVERSITY OF NEBRASKA; MILLER, JAMES - LOUISIANA STATE UNIVERSITY; MORGAN, JAMES - ROUND MOUNTAIN CONSULTING; Rosen, Benjamin - Ben; Van Tassell, Curtis - Curt; NOTTER, DAVID - VIRGINIA TECH; MURDOCH, BRENDA - UNIVERSITY OF IDAHO

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2022
Publication Date: 3/10/2022
Citation: Becker, G.M., Burke, J.M., Lewis, R.M., Miller, J.E., Morgan, J.L., Rosen, B.D., Van Tassell, C.P., Notter, D.R., Murdoch, B. 2022. Variants within genes EDIL3 and ADGRB3 are associated with divergent fecal egg counts in Katahdin sheep at weaning. Frontiers in Genetics. https://doi.org/10.3389/fgene.2022.817319.
DOI: https://doi.org/10.3389/fgene.2022.817319

Interpretive Summary: Gastrointestinal nematodes (GIN) pose a severe threat to sheep production worldwide. Anthelmintic drug resistance coupled with growing concern regarding potential environmental effects of drug use have demonstrated the necessity of implementing other methods of GIN control. The aim of this study was to test for genetic variants associated with resistance or susceptibility to GIN in Katahdin sheep to improve the current understanding of the genetic mechanisms responsible for host response to GIN. A genome-wide association study was conducted with high density genotype data and cube-root transformed weaning fecal egg counts (tFEC) of 583 Katahdin sheep. Four significant SNPs (P-values 7.82e-08 to 3.34e-08) were identified within the first intron of the gene EGF-like repeats and discoidin domains 3 (EDIL3). These identified SNPs were in very high linkage disequilibrium (r2 of 0.996 to 1), and animals with alternate homozygous genotypes had significantly higher median weaning tFEC phenotypes compared to all other genotypes. Significant SNPs were queried through public databases to identify putative transcription factor binding site (TFBS) and potential lncRNA differences between reference and alternate alleles. Changes in TFBS were predicted at two SNPs, and one significant SNP was found to be within a predicted lncRNA sequence with greater than 90% similarity to a known lncRNA in the bovine genome. The gene EDIL3 has been described in other species for its roles in the inhibition and resolution of inflammation. Potential changes of EDIL3 expression mediated through lncRNA expression and/or transcription factor binding may impact the overall immune response and reduce the ability of Katahdin sheep to control GIN infection. This study lays the foundation for further research of EDIL3 towards understanding genetic mechanisms of susceptibility to GIN, and suggests these SNPs may contribute to genetic strategies for improving parasite resistance traits in sheep.

Technical Abstract: Genetic resistance of sheep to gastrointestinal nematodes is an important technology to manage these parasites, but the genomic mechanisms of resistance are not well understood. Scientists from University of Idaho, Agricultural Research Service - Booneville, AR and Beltsville, MD, University of Nebraska-Lincoln, Louisiana State University, Round Mountain Katahdin, and Virginia Tech used genomic techniques to identify SNP or genetic information that differed between susceptible and resistant Katahdin sheep. A gene (EDIL3) that is associated with inflammation response was thought to be involved. This information is important to sheep producers, scientists, veterinarians, and extension specialists aiming to minimize parasite problems in sheep.