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Background  Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene ( PRNP)  whereas atypical scrapie susceptibility is related to polymorphisms at codon 141. Many other variants over the length of the  PRNP  have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and  PRNP  characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s  PRNP  gene has socioeconomic and scientific merits. This study aimed to identify  PRNP  variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility.    Results  Five novel variants were identified in the  PRNP  gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-- > CAA), H99L (CAC-- > CTA), A116E (GCA-- > GAA), A116T (GCA-- > ACA), and one synonymous N103 N (AAC-- > AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study.    Conclusion  Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141 L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.

Five novel PRNP gene polymorphisms and their potential effect on Scrapie susceptibility in three native Ethiopian sheep breeds