Browsing by Author "Murdoch, Brenda M."
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- Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheepBecker, G. M.; Davenport, K. M.; Burke, Joan M.; Lewis, R. M.; Miller, James E.; Morgan, James L. M.; Notter, David R.; Murdoch, Brenda M. (2020-01-03)Resistance to gastrointestinal nematodes has previously been shown to be a moderately heritable trait in some breeds of sheep, but the mechanisms of resistance are not well understood. Selection for resistance currently relies upon faecal egg counts (FEC), blood packed cell volumes and FAMACHA visual indicator scores of anaemia. Identifying genomic markers associated with disease resistance would potentially improve the selection process and provide a more reliable means of classifying and understanding the biology behind resistant and susceptible sheep. A GWAS was conducted to identify possible genetic loci associated with resistance to Haemonchus contortus in Katahdin sheep. Forty animals were selected from the top and bottom 10% of estimated breeding values for FEC from a total pool of 641 sires and ram lambs. Samples were genotyped using Applied Biosystems (TM) Axiom (TM) Ovine Genotyping Array (50K) consisting of 51 572 SNPs. Following quality control, 46 268 SNPs were included in subsequent analyses. Analyses were conducted using a linear regression model in plink v1.90 and a single-locus mixed model in snp and variation suite. Genome-wide significance was determined by a Bonferroni correction for multiple testing. Using linear regression, loci on chromosomes 2, 3, 16, 23 and 24 were significantly associated at the genome level with FEC estimated breeding values, and we identified a region on chromosome 2 that was significant using both statistical analyses. We suggest a potential role for the gene DIS3L2 for gastrointestinal nematode resistance in Katahdin sheep, although further research is needed to validate these findings.
- Single Nucleotide Polymorphism Effects on Lamb Fecal Egg Count Estimated Breeding Values in Progeny-Tested Katahdin SiresNotter, David R.; Heidaritabar, Marzieh; Burke, Joan M.; Shirali, Masoud; Murdoch, Brenda M.; Morgan, James L. M.; Morota, Gota; Sonstegard, Tad S.; Becker, Gabrielle M.; Spangler, Gordon L.; MacNeil, Michael D.; Miller, James E. (Frontiers, 2022-05-03)Estimated breeding values (EBV) for fecal egg counts (FEC) at 42-90 days of age (WFEC) and 91-150 days of age (PFEC) for 84 progeny-tested Katahdin sires were used to identify associations of deregressed EBV with single-nucleotide polymorphisms (SNP) using 388,000 SNP with minor-allele frequencies >= 0.10 on an Illumina high-density ovine array. Associations between markers and FEC EBV were initially quantified by single-SNP linear regression. Effects of linkage disequilibrium (LD) were minimized by assigning SNP to 2,535 consecutive 1-Mb bins and focusing on the effect of the most significant SNP in each bin. Bonferroni correction was used to define bin-based (BB) genome- and chromosome-wide significance. Six bins on chromosome 5 achieved BB genome-wide significance for PFEC EBV, and three of those SNP achieved chromosome-wide significance after Bonferroni correction based on the 14,530 total SNP on chromosome 5. These bins were nested within 12 consecutive bins between 59 and 71 Mb on chromosome 5 that reached BB chromosome-wide significance. The largest SNP effects were at 63, 67, and 70 Mb, with LD among these SNP of r(2) <= 0.2. Regional heritability mapping (RHM) was then used to evaluate the ability of different genomic regions to account for additive variance in FEC EBV. Chromosome-level RHM indicated that one 500-SNP window between 65.9 and 69.9 Mb accounted for significant variation in PFEC EBV. Five additional 500-SNP windows between 59.3 and 71.6 Mb reached suggestive (p < 0.10) significance for PFEC EBV. Although previous studies rarely identified markers for parasite resistance on chromosome 5, the IL12B gene at 68.5 Mb codes for the p40 subunit of both interleukins 12 and 23. Other immunoregulatory genes are also located in this region of chromosome 5, providing opportunity for additive or associative effects.
- Using whole genome sequence to compare variant callers and breed differences of US sheepStegemiller, Morgan R.; Redden, Reid R.; Notter, David R.; Taylor, Todd; Taylor, J. Bret; Cockett, Noelle E.; Heaton, Michael P.; Kalbfleisch, Theodore S.; Murdoch, Brenda M. (Frontiers, 2023-01-04)As whole genome sequence (WGS) data sets have become abundant and widely available, so has the need for variant detection and scoring. The aim of this study was to compare the accuracy of commonly used variant calling programs, Freebayes and GATK HaplotypeCaller (GATK-HC), and to use U.S. sheep WGS data sets to identify novel breed-associated SNPs. Sequence data from 145 sheep consisting of 14 U.S. breeds were filtered and biallelic single nucleotide polymorphisms (SNPs) were retained for genotyping analyses. Genotypes from both programs were compared to each other and to genotypes from bead arrays. The SNPs from WGS were compared to the bead array data with breed heterozygosity, principal component analysis and identifying breed associated SNPs to analyze genetic diversity. The average sequence read depth was 2.78 reads greater with 6.11% more SNPs being identified in Freebayes compared to GATK-HC. The genotype concordance of the variant callers to bead array data was 96.0% and 95.5% for Freebayes and GATK-HC, respectively. Genotyping with WGS identified 10.5 million SNPs from all 145 sheep. This resulted in an 8% increase in measured heterozygosity and greater breed separation in the principal component analysis compared to the bead array analysis. There were 1,849 SNPs identified in only the Romanov sheep where all 10 rams were homozygous for one allele and the remaining 135 sheep from 13 breeds were homozygous for the opposite allele. Both variant calling programs had greater than 95% concordance of SNPs with bead array data, and either was suitably accurate for ovine WGS data sets. The use of WGS SNPs improved the resolution of PCA analysis and was critical for identifying Romanov breed-associated SNPs. Subsets of such SNPs could be used to estimate germplasm composition in animals without pedigree information.
- Variants Within Genes EDIL3 and ADGRB3 are Associated With Divergent Fecal Egg Counts in Katahdin Sheep at WeaningBecker, Gabrielle M.; Burke, Joan M.; Lewis, Ronald M.; Miller, James E.; Morgan, James L. M.; Rosen, Benjamin D.; Van Tassell, Curtis P.; Notter, David R.; Murdoch, Brenda M. (Frontiers, 2022-03-10)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 (r(2) 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.