Genome-wide association study of a thermo-tolerance indicator in pregnant ewes exposed to an artificial heat-stressed environment

Environmental heat stress negatively influences sheep production in warm semi-arid regions. An animal's ability to tolerate warm weather is difficult to measure naturally due to environmental variability and genetic variation between animals. In this study we developed a thermo-tolerance indicator (TTI) to define heat stress tolerance in pregnant sheep in a controlled environment. Next, we performed a genome-wide association study (GWAS) to identify genomic regions and target genes associated with thermo-tolerance in sheep. Pregnant Columbia-Rambouillet crossbred ewes (n = 127) were heat-stressed inside a climate-controlled chamber for 57 days by increasing the temperature-humidity index to ≥30. Rectal temperature (RT) and feed intake (FI) data were collected daily and used for the predictive TTI analysis. After the tenth day of heat stress, the regression analyses revealed that FI was stable; however, when the ewe's RT exceeded 39.8 °C their FI was less than thermo-tolerant ewes. This average predicted temperature was used to classify each ewe as heat stress tolerant (≤39.8 °C) and non-heat stress tolerant (>39.8 °C). A GWAS analysis was performed and genomic regions were compared between heat stress tolerant and non-tolerant ewes. The single-marker genomic analysis detected 16 single nucleotide polymorphisms (SNP) associated with heat stress tolerance (P < 0.0001), whereas the multi-marker Bayesian analysis identified 8 overlapped 1-Mb chromosomal regions accounting for 11.39% of the genetic variation associated with tolerance to heat stress. Four intragenic SNP showed a remarkable contribution to thermo-tolerance, and these markers were within the genes FBXO11 (rs407804467), PHC3 (rs414179061), TSHR (rs418575898) and STAT1 (rs417581105). In conclusion, genomic regions harboring four intragenic SNP were associated with heat stress tolerance, and these candidate genes are proposed to influence heat tolerance in pregnant ewes subjected to an artificially induced warm climate. Moreover, these genetic markers could be suitable for use in further genetic selection programs in sheep managed in semi-arid regions.