A high-density genome-wide association with absolute blood monocyte count in domestic sheep identifies novel loci

Authors: OLIVEIRA, RYAN - Washington State University; Mousel, Michelle; GONZALEZ, MICHAEL - The Children'S Hospital Of Philadelphia; Durfee, Codie; DAVENPORT, KIMBERLY - University Of Idaho; MURDOCH, BRENDA - University Of Idaho; Taylor, Joshua - Bret; NEIBERGS, H - Washington State University; White, Stephen

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2022
Publication Date: 5/6/2022
Citation: Oliveira, R.D., Mousel, M.R., Gonzalez, M.V., Durfee, C.J., Davenport, K.M., Murdoch, B.M., Taylor, J.B., Neibergs, H.L., White, S.N. 2022. A high-density genome-wide association with absolute blood monocyte count in domestic sheep identifies novel loci. PLoS ONE. 17(5). Article e0266748. https://doi.org/10.1371/journal.pone.0266748.
DOI: https://doi.org/10.1371/journal.pone.0266748

Interpretive Summary: Monocytes are an essential part of the immune system and can differentiate into cells responsible for phagocytosis and antigen presentation which are crucial components of the adaptive immune response. These cells can both control and propagate infectious diseases such as Coxiella burnetii and small ruminant lentivirus in sheep. Four hundred eighty Rambouillet, Polypay, and Columbia sheep were geneotype at a high density or had high density genotypes imputed to test for genomic regions associated with blood monocyte count. Two genome-wide significant associations were identified on chromosomes 9 and 1, and ten genome-wide suggestive associations were found on chromosomes 1, 2, 3, 4, 9, 10, 15, and 16. Genes within or near association peaks were involved in cytokine production, subsetting monocyte lineages, and marking stages of bone marrow myeloid cell development. Investigating the genetic basis of monocyte lineages and counts may provide information about pathogens of veterinary importance and elucidate fundamental immunology.

Technical Abstract: Monocytes are a core component of the immune system that arise from the blood marrow and differentiate into cells responsible for phagocytosis and antigen presentation. They are essential to the immune system, and their derivatives are often responsible for beginning the adaptive immune response. Monocytes and macrophages are central in both controlling and propagating infectious diseases such as infection by Coxiella burnetii and small ruminant lentivirus in sheep. Genotypes from 513 Rambouillet, Polypay, and Columbia sheep (Ovis aries) were generated using the Ovine SNP50 Infinium® BeadChip. Of this group, 222 animals were subsequently genotyped with the Ovine Infinium® HD SNP BeadChip to increase SNP coverage. This group of 222 sheep was combined with a separate group of 258 sheep to form a 480-sheep reference panel used to impute the low-density sheep to the HD genotyping density. These data were then used to perform a genome-wide association analysis to identify loci associated with absolute monocyte counts from blood. The analysis used a single-locus mixed linear model implementing EMMAX with age and ten principal components as fixed effects. Two genome-wide significant peaks (p < 5x10-7) were observed on chromosomes 9 and 1, and ten genome-wide suggestive peaks (p < 1x10-5) were observed on chromosomes 1, 2, 3, 4, 9, 10, 15, and 16. Some peaks included genes involved in cytokine production, sub-setting monocyte lineages, and marking stages of bone marrow myeloid cell development. These loci are being further investigated to understand their contributions to monocyte counts. Investigating the genetic basis of monocyte lineages and numbers may in turn provide information about pathogens of veterinary importance and elucidate fundamental immunology.