The aim of this study is to investigate the profile of ovine PrP gene by amino acid polymorphism at codons 136, 141, 154, and 171 for determining the genetic predisposition to the Scrapie disease for the tribal sheep and rams, with different numbers and distribution in Bulgaria. Three hundred twenty four animals originating from 41 tribal herds comprising eight breeds were included in the study. DNA was isolated from blood samples specifically amplified by PCR and sequenced. The alignments of codons 136, 141, 154, and 171 were determined. Based on the sequencing, it was established that Bulgarian breeds belong to the second and third risk groups, those with low and moderate risk of Scrapie disease. Establishment of 11 genotypes in Synthetic Population Bulgarian Milk breed reveals it to have the highest risk of the Scrapie disease; moreover, the conducting of the program will be more difficult in comparison with other investigated breeds. Evidence for the internal cross breeding is the presence of the five or six genotypes in the Copper-Red Shoumen, Replian, Karakachan, and Duben Bulgarian native breeds.