Characterisation of the PRNP gene polymorphisms in Zom sheep

Aim of study: Polymorphisms in codons 136, 154, and 171 of the prion protein gene (PRNP) are critical due to their association with susceptibility or resistance to scrapie, a fatal neurodegenerative disease in sheep. This study aimed to analyze the genetic diversity of PRNP in Zom sheep, an indigenous breed of Türkiye, and to evaluate its potential implications for scrapie resistance. Area of study: Türkiye. Material and methods: Genomic DNA was extracted from blood samples of 46 Zom sheep. A 662 bp region of the PRNP gene was amplified using polymerase chain reaction (PCR) and sequenced. Allele and genotype frequencies of the identified polymorphisms were calculated. The potential functional effects of missense single nucleotide polymorphisms (SNPs) were predicted using PolyPhen-2, PANTHER, and AMYCO bioinformatics tools. Haplotype analysis was also performed to assess genetic variation. Main results: Five alleles and six genotypes were identified. The ARQ allele, ARQ/ARQ and ARR/ARQ genotypes were predominant, while resistance-associated alleles and genotypes were less frequent. Ten polymorphisms were identified, including one insertion/deletion variant and six missense SNPs leading to amino acid substitutions. PolyPhen-2 classified T195I, T196S, and N146S as benign, while T193S was predicted as possibly damaging and V179G as probably damaging. PANTHER predicted all scorable SNPs as possibly damaging, whereas AMYCO found no amyloidogenic risk. Additionally, twelve haplotypes were identified within the population. Research highlights: This study provides population-level data on PRNP polymorphisms in Zom sheep, suggesting a potential link to partial resistance to scrapie and offering insights for future breeding approaches.