Discovery of host genetic factors through multi-locus GWAS against toxoplasmosis in sheep: addressing one health perspectives

Toxoplasma gondii stands as one of the most successful pathogens, capable of infecting nearly all warm-blooded species. It is estimated that up to 50% of human population might harbor Toxoplasmosis infections. One of the primary transmission routes is the consumption of tissue cysts from infected farm animals used for food production. Thus, controlling Toxoplasmosis in farm animals is of vital importance for human health and food safety. Selective breeding in farm animals, where available, could complement classical control measures like biosecurity measures, vaccination, and test-and-cull methods. This multidisciplinary approach will make the eradication of Toxoplasmosis more effective. For this purpose, we conducted four multi-locus genome-wide association (GWA) approaches to identify the polygenic factors underlying innate resistance to Toxoplasma gondii in naturally infected sheep. Our findings indicate that 16 single nucleotide polymorphisms (SNPs), exhibiting varying degrees of statistical power, play a significant role in host immunity against T. gondii infection. We propose the genes containing these SNPs or located within 100 ± Kb of them (PLSCR5, EPHA3, DGKB, IL12B, CGA, WDR64, TMEM158, CLMP, and SIAE) as potential candidate genes. This study represents the first exploration of host genetic factors against Toxoplasmosis in livestock, utilizing the ovine paradigm as its foundation.