Genome-wide insights on gastrointestinal nematode resistance in autochthonous Tunisian sheep

Abstract

Gastrointestinal nematode (GIN) infections have negative impacts on animal health, welfare and production. Information from molecular studies can highlight the underlying genetic mechanisms that enhance host resistance to GIN. However, such information often lacks for traditionally managed indigenous livestock. Here, we analysed 600 K single nucleotide polymorphism genotypes of GIN infected and non-infected traditionally managed autochthonous Tunisian sheep grazing communal natural pastures. Population structure analysis did not find genetic differentiation that is consistent with infection status. However, by contrasting the infected versus non-infected cohorts using ROH, LR-GWAS, FST and XP-EHH, we identified 35 candidate regions that overlapped between at least two methods. Nineteen regions harboured QTLs for parasite resistance, immune capacity and disease susceptibility and, ten regions harboured QTLs for production (growth) and meat and carcass (fatness and anatomy) traits. The analysis also revealed candidate regions spanning genes enhancing innate immune defence (SLC22A4, SLC22A5, IL-4, IL-13), intestinal wound healing/repair (IL-4, VIL1, CXCR1, CXCR2) and GIN expulsion (IL-4, IL-13). Our results suggest that traditionally managed indigenous sheep have evolved multiple strategies that evoke and enhance GIN resistance and developmental stability. They confirm the importance of obtaining information from indigenous sheep to investigate genomic regions of functional significance in understanding the architecture of GIN resistance.

Genome variation in tick infestation and cryptic divergence in Tunisian indigenous sheep

“…We analysed the data with ROH, LR-GWAS, XP-EHH and F ST , to investigate signatures of selection associated with variation in tick infestation and thus possible resistance. As noted by [ 52 ], we also acknowledge that using naturally infected animals to study the genetic basis of resistance runs the risk of resistant animals being a cocktail of truly highly resistant individuals as well as those that were never exposed to infestations/infections. These factors may dilute the certainty that animals showing high or low resistance to different pathogens and parasites, could in fact be functionally dissimilar [ 52 ].…”

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

“…The biguanide metformin has been found to reach higher plasma concentration in octn1 knockout mice with respect to wild-type ones after low dose administration. On the contrary, lower plasma concentration levels of the drug were found in octn1 knockout after high dose administration [ 30 ]. After intravenous administration, elimination of metformin was similar in the two strains.…”

“…At lower dose, the transporter might be involved in intestinal metformin efflux, not uptake. In contrast, in the kidney, OCTN1 does not seem to be implicated in metformin excretion, considering that minimal differences in renal distribution between wild-type and knockout mice were observed [ 30 ].…”

The natural adaptation and human selection history of African sheep genomes

“…In arid environments, feed, water and heat stress can also weaken immunity (Silanikove 2000). The candidate region on OAR11 that spanned four genes (NF1, EVI2A, EVI2B, OMG) associated with tail morphology, has also been linked to gastrointestinal nematode infection resistance in traditionally managed Tunisian sheep (Ahbara et al, 2021). The PDGFRA gene that occurred in a candidate region on OAR6, and which has been associated with the fat-tail phenotype (Mastrangelo et al, 2019) likely through the differentiation of preadipocytes, has also been implicated in host immune responses against endoparasites and is a key gene in cytokine signaling (Beh et al, 2002;Benavides et al, 2015).…”

“…Hp, XP-EHH Plays an essential role in the infection stages of Trypanosoma brucei by maintaining its mitochondrial integrity (Nowikovsky et al, 2012;Hashimi et al, 2013;Nowikovsky and Bernardi, 2014) 18250001-18490000 11 NF1, EVI2A, EVI2B, OMG FST, XP-EHH Linked to gastrointestinal nematode infection resistance in traditionally managed Tunisian sheep (Ahbara et al, 2021)…”