A novel T177P missense variant in the HSPA8 gene associated with the low tolerance of Awassi sheep to heat stress.

Abstract

This study was conducted to identify the association of coding variations in the HSPA8 gene with heat stress in two different breeds of sheep. All the coding regions of the HSPA8 gene of Awassi and Arabi sheep were covered by amplifying nine exons. A single-strand conformation polymorphism (SSCP) was utilized to assess the genetic variations in both breeds. The possible association of the observed genotypes with rectal temperature (RT), respiratory rate (RR), and heat tolerance coefficient (HTC) was analyzed in different seasons. While all the coding regions of both sheep were monomorphous, a remarkable heterogeneity was observed in exon 4, of which two SSCP patterns, a normal TT and a mutant TG, were detected. The TG genotype was characterized by a missense variant of T177P with frequencies of 77% in Awassi and 54% in Arabi. Cumulative in silico tools indicated extremely deleterious consequences for T177P on protein structure, function, and stability. Results indicated that sheep with the TT genotype had significantly (P< 0.05) lower RT, RR, and HTC values than sheep with the TG genotype. Therefore, a significant association of T177P with a lower tolerance of Awassi to higher temperature conditions was revealed. In conclusion, the identified T177P may have damaging effects in the HSPA8, which affects the ability of Awassi sheep to cope up with elevated temperatures compared with Arabi sheep. This manuscript describes a novel description of a highly deleterious missense variant in the HSPA8 gene that may reduce the ability of sheep to withstand high-temperature conditions.