Characterization of PRNP and SPRN coding regions from atypical scrapie cases diagnosed in Poland

Abstract

Scrapie, a fatal transmissible spongiform encephalopathy (TSE) occurs in two phenotypes: classical and atypical. Many authors point out that the polymorphism of three codons (136, 154, 171) of the PRNP (PrP gene) is associated with a sheep susceptibility to classical scrapie. Until now, only one PRNP gene variant coding phenylalanine at codon 141 has been found to be associated with atypical scrapie. Another recently identified and interesting candidate gene for scrapie susceptibility in sheep is an SPRN gene coding for Shadoo protein (Sho). Sho is a highly interspecies conserved protein and an insertion/deletion (indel) found in a sheep Sho gene was associated with classical scrapie occurrence. Here we determined the polymorphism of PRNP and SPRN genes in nine atypical scrapie cases (six in native born sheep and three in imported sheep) and compared these results with a control group of healthy animals comprising six corresponding Polish sheep breeds. In atypical scrapie cases five PRNP diplotypes were identified: A(136)R(154)Q(171)/ARQ, AHQ/ARQ, ARR/ARQ, ARR/AHQ and AHQ/AHQ. The ARR/AHQ diplotype was found only in imported sheep. A previously unobserved SNP in PRNP (E224K) was also found in both atypical scrapie and in a few control animals. In the ORF of the SPRN gene, six SNPs and one indel were identified. None of these variations was exclusive for scrapie animals and they were probably, naturally occurring polymorphisms. Special attention was given to the 6-bp indel SPRN polymorphism which was previously associated with classical scrapie occurrence.

Genotyping and surveillance for scrapie in Finnish sheep

“…The importance of the relatively high frequency of R151C in Finnish Landrace is unknown. The dimorphism of E224K found in Finnish Landrace (5.8%) and Grey race sheep of Kainuu (18.8%) has recently been described in Polish sheep breeds [18]. To our knowledge the study of Piestrzynska-Kajtoch et al (2012) and this study are the only reports of E224K polymorphism so far.…”

“…Altogether eight dimorphisms out of 410 sheep samples sequenced in full, specifically G89S, M137T, H143R, R151C, R211Q, Q220L, E224K and P241S, were detected. All of them except Q220L have been described before [5,10,16-18]. The most common dimorphisms detected in Finnish Landrace sheep were R151C and E224K with allele frequencies 6.6% and 5.8%, respectively.…”

“…The most frequent polymorphisms present in Finnish Landrace were R151C and E224K (6.6 and 5.8% of sheep studied, respectively), both of which have been described before [17,18,29]. Variation in ovine PrP gene is common, but an association of these polymorphisms with scrapie is mostly unknown [11].…”