Novel Prion Protein Gene Polymorphisms in Awassi Sheep in Three Regions of the Fertile Crescent

SIMPLE SUMMARY: The Awassi sheep is the most widely bred fat-tail sheep in the Near and Middle East. In this research, a total of 150 healthy Awassi sheep from Türkiye, the Palestinian Authority, and Saudi Arabia were screened for variants in the prion protein gene (PRNP). Genotyping Awassi sheep for the prion protein gene allowed us to assess the level of genetic susceptibility to scrapie in studied populations. In addition, twenty-seven amino acid substitutions were found. Eight of them have not been previously reported. Our results on Awassi sheep may assist selection programs that aim to increase the scrapie-resistant genotypes in the populations to reduce the risk of scrapie. ABSTRACT: Scrapie is a fatal, neurodegenerative disease that affects sheep and goats, and genetic susceptibility to scrapie in sheep is associated with polymorphisms in the prion protein (PRNP) gene. The aim of this study is to identify PRNP polymorphism in Awassi sheep from Türkiye, the Palestinian Authority, and Saudi Arabia. A total of 150 healthy sheep were genotyped for PRNP, using Sanger sequencing. There were seven alleles and eleven genotypes observed based on codons 136, 154, and 171 of PRNP. The ARQ allele was predominant in all populations. The most resistant allele to scrapie, ARR, was present in all three regions. The VRQ allele, associated with the highest susceptibility to scrapie, was detected only in Türkiye at a low frequency. In this study, twenty-seven amino acid substitutions were found. Eight of them (R40Q, G65E, H88L, S98T, A118P, S138T, V192F and L250I) have not been previously reported. These data indicate that sheep breeds close to the sheep domestication center have maintained high genetic diversity in the PRNP region. Our findings on PRNP will provide valuable insights for sheep breeding programs, aiding in the selection of genotypes resistant to scrapie in Türkiye, the Palestinian Authority, and Saudi Arabia.