Grossman, P. C. | Search bioRxiv

bioRxiv2025

Bighorn sheep T2T genome assembly reveals differences in immune genes: a potential cause of high morbidity due to respiratory pathogens

The bighorn sheep (Ovis canadensis), despite its close relation to domestic sheep, suffer higher morbidity and mortality from respiratory disease complexes, likely due to genetic differences in immune responses. Unraveling highly repetitive regions such as immune loci and genetic differences was problematic until now. We generated a bighorn sheep telomere-to-telomere assembly, adding 14.28% of novel sequence compared to the previous reference. This enabled the first complete immune loci annotation revealing the IGL and TR loci are significantly short in bighorn sheep. Importantly, a critical immune gene GBP5 and ZNF501, involved in Golgi-mediated immune response, are lacking in bighorn but present in domestic sheep. Re-analysis of a Mycoplasma ovipneumoniae carriage study, using this assembly, identified the immune gene CAPN2 as a key genetic marker for disease carriage, not observable in the original study. This work provides a critical resource for identifying phenotype-linked genetic variation and exploring evolutionary adaptations of bighorn sheep.

genomics↗

bioRxiv2019

Differential pulmonary immunopathologic response of domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) to Mycoplasma ovipneumoniae infection: a retrospective study

Mycoplasma ovipneumoniae is a respiratory pathogen that can impact domestic sheep (Ovis aries; DS) and bighorn sheep (Ovis canadensis; BHS). Experimental and field data have indicated BHS are more susceptible than DS to developing polymicrobial pneumonia associated with Mycoplasma ovipneumoniae infection. We hypothesized that DS and BHS have a differential immunopathologic pulmonary response to M. ovipneumoniae infection. A retrospective study was performed using formalin-fixed, paraffin-embedded (FFPE) lung tissue from DS and BHS without and with M. ovipneumoniae detected in the lung tissue (n=8 per group). While each M. ovipneumoniae positive lung sample had microscopic changes typical of infection, including hyperplasia of intrapulmonary bronchus-associated lymphoid tissue (BALT) and respiratory epithelium, DS exhibited a more robust and well-organized BALT formation as compared to BHS. Immunohistochemistry was performed with antibodies reactive in FFPE tissues and specific for leukocyte and cytokine markers: T cell marker CD3, B cell markers CD20 and CD79a, macrophage markers CD163 and Iba1, and cytokine IL-17. Digital analysis was used to quantitate chromogen deposition in regions of interest (ROIs), including alveolar and bronchiolar areas, and bronchiolar subregions (epithelium and BALT). Main effects and interaction of species and infection status were analyzed by beta regression and Bonferroni corrections were performed on pairwise comparisons (PBon<0.05 significance). Significant species differences were identified for bronchiolar CD3 (PBon=0.0023) and CD163 (PBon=0.0224), alveolar CD163 (PBon=0.0057), and for IL-17 in each of the ROIs (alveolar: PBon=0.0009; BALT: PBon=0.0083; epithelium: PBon=0.0007). Infected BHS had a higher abundance of bronchiolar CD3 (PBon=0.0005) and CD163 (PBon=0.0162), and alveolar CD163 (PBon=0.0073). While IL-17 significantly increased with infection in BHS BALT (PBon=0.0179) and alveolar (0.0006) ROIs, abundance in DS showed an insignificant decrease in these ROIs and a significant decrease in epithelial abundance (PBon=0.0019). These findings support the hypothesis that DS and BHS have a differential immunopathologic response to M. ovipneumoniae infection.

immunology↗