Variants Within Genes EDIL3 and ADGRB3 are Associated With Divergent Fecal Egg Counts in Katahdin Sheep at Weaning

Abstract

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. Linear regression and case-control genome-wide association studies were conducted with high-density genotype data and cube-root transformed weaning fecal egg counts (tFEC) of 583 Katahdin sheep. The case-control GWAS identified two significant SNPs (P-values 1.49e-08 to 1.01e-08) within introns of the gene adhesion G protein-coupled receptor B3 (ADGRB3) associated with lower fecal egg counts. With linear regression, 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 0.996–1), 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 and ADGRB3 towards understanding genetic mechanisms of susceptibility to GIN, and suggests these SNPs may contribute to genetic strategies for improving parasite resistance traits in sheep.

New insights into the novel sequences of the chicken pan-genome by liquid chip

“…This indicated the reliability of our results and the efficacy of the liquid chip for GWAS. For immune traits, SNPs on adhesion G protein-coupled receptor B3 ( ADGRB3 ) were associated with the H/L ratio, and this gene was associated with fecal egg counts in sheep ( Becker et al, 2022 ). For novel sequences, no significant SNPs were associated with BW or immune-related traits at the genome-wide level.…”

Genomic Regions Associated with Resistance to Gastrointestinal Nematode Parasites in Sheep—A Review

“…One approach to understanding the genetic basis of traits is performing a genomewide association study (GWAS) to identify significant genetic markers, more recently single nucleotide polymorphisms (SNPs) associated with a trait. Recent studies have conducted a GWAS for resistance to GINs in sheep using SNP panels [6,[23][24][25][26][27][28][29][30][31][32]. However, in the early 2000s, before the availability of SNP panels, studies performing association analysis used microsatellite markers [33][34][35][36][37][38][39].…”

“…Several results have been found regarding genomic regions, candidate genes, and quantitative trait loci (QTLs) associated with several traits related to resistance to GINs in sheep. In addition to the number of results produced in past years, little consensus has been achieved regarding the major genes and similar genomic regions affecting traits related to resistance to GINs in different sheep breeds or populations [1,6,23].…”

A computational framework for improving genetic variants identification from 5,061 sheep sequencing data

“…Genetic variation refers to differences in the genetic makeup of individuals in the same species. Single nucleotide polymorphisms (SNPs) and insertions/deletions (Indels) are two common types of genetic variants among individuals [ 1 ], which contribute to genetic diversity and critically influence phenotypic differences, including diseases susceptibility in human [ 2 – 4 ], trait enhancement and disease resistance in animal and plant breeding [ 5 – 7 ]. The genetic variants related to the phenotypes can be used to inform disease prediction [ 4 ], identification of causal mechanisms of disease [ 2 ], and the prioritization of biological targets in breeding programs in plants and animals [ 6 , 7 ].…”