Abstract
Background: Classical Scrapie susceptibility in sheep has been linked to three polymorphisms at positions 136, 154, and 171 in the PRNP gene whereas atypical scrapie susceptibility is related to a polymorphism at position 141. Many other variants over the length of the prion protein coding gene were reported. Since infectious prion protein itself seems to be polymorphic, the identified novel PRNP gene variations may play a crucial role in fighting against the emergence of a new form of scrapie disease. Many studies conducted around the world to identify disease resistant status and new variants of PRNP gene in different breeds. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breeds PRNP gene provides essential information to the current knowledge. This study aimed to identify potential novel variations in the Ethiopian sheep PRNP gene, thereby determine the uniqueness of the native breeds and predict scrapie status of sheep population based on the genotypes distribution. Results : Five novel variants were identified in the PRNP gene of native Ethiopian sheep. Four non-synonymous heterozygous substitutions at H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) variants were detected. In addition to the novel variations, polymorphisms at 126,127,138,142,146,231, and 237 positions were also identified. The haplotype ARR was observed only in Menz and Afar breeds with frequencies 0.02 and 0.05 respectively. However, neither ARR/ARR nor VRQ/VRQ genotypes were identified in all of the breeds. Conclusion: Two of the novel variations at position 99 and 103 that are placed closer to the cleavage site and variant at 116 spotted in the palindrome region along with variants at position 127 in Glycine repeat domain may influence the conformational flexibility of prion protein. The low frequency of ARR haplotype and the sole variant 141L demonstrated that Ethiopian sheep are susceptible to classical scrapie and resistant to atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies against scrapie during inbreeding, crossbreeding and help to take precautious measures.
Novel Variations at Three Different Positions of Prion Protein Coding Gene in Ethiopian Sheep Breeds and the Resistance/Susceptible Status to Classical and Atypical Scrapie
