Submitted to: American Journal of Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2005
Publication Date: 8/1/2005
Citation: Evoniuk, J.M., Stoltenow, C.L., O'Rourke, K.I., Moore, B.L., Redmer, D.A. 2005. Assessment of the genetic risk and impact of lateral transmission in a valine-associated scrapie outbreak in sheep. American Journal of Veterinary Research. 66(8):1-6. Interpretive Summary: Scrapie is a fatal neurologic disease of sheep, endemic in the US but the subject of a vigorous eradication program. Scrapie is associated with accumulation of a misfolded form of the sheep prion protein. Control measures in an infected flock include removal of all genetically susceptible sheep. Susceptibility is controlled by naturally occurring differences in the prion protein, designated 171Q (susceptible) or 171R (generally resistant). The resistance of sheep with the 171R form of the gene occurs with one scrapie strain, the most US strain, but these sheep are not protected from the alternative strain, identified as valine associated scrapie. Anecdotal reports have shown that the strain probably occurs in the US but is relatively rare. In this publication, the presence of the valine associated strain was demonstrated through epidemiology and genetic analysis of a large flock of sheep. The study demonstrated that this scrapie strain can infect sheep as adults and is spread efficiently among related and unrelated sheep housed together during lambing seasons. The results suggest that the outbreak was due to the relatively high number of sheep with the susceptible form of the gene, probably introduced through the use of highly prolific rams carrying the gene. Further, transmission of the disease among adults, the prolonged incubation time, the unsuitability of some susceptible sheep to live animal testing, and susceptibility of sheep with the 171R gene suggest that removal of sheep with the genotype AVQR from infected flocks would be prudent.
Technical Abstract: Scrapie is a member of the heterogenous family of transmissible spongiform encephalopathies. Although these disorders appear to be related to misfolding of a host protein rather than an exogenous organism, two distinct disease phenotypes or strains are noted in sheep. Characterization of the scrapie strains in experimental and field settings in the United Kingdom and Europe have included differences in incubation time, survival rates, lateral transmission efficiency and most importantly, genetic susceptibility. Sheep of the prototype strain SSPB/1 are susceptible only if the PRNP (prion protein precursor gene) encodes valine (V) at codon 136; a polymorphism (encoding glutamine to arginine) at codon 171 apparently reduces disease prevalence but increases incubation time and limits tissue distribution to the brain. Sheep with the prototype valine-independent strain CH1641 are susceptible only if homozygous for glutamine (Q) at codon 171. In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641. The only genotype useful for strain discrimination is the relatively rare 136AV/171QR. In this study, a flock of sheep with a large number of infected sheep was analyzed. The presence of at least one V136 allele was identified in all but 2 sheep in the study, incubation times were very short in V136 homozygous sheep, probable lateral transmission was demonstrated in 15 sheep, and at least one AVQR sheep was identified. Therefore, this outbreak was probably due to a valine-associated (SSBP/1-like) strain and this report is the first full description of the epidemiology of this strain in US sheep. The high rate of lateral transmission and the susceptibility of 136AV/171QR sheep to scrapie suggest that genotyping for codon 136 may assist management decisions following a scrapie diagnosis and that it may be prudent to remove sheep of the 136AV/171QR genotype from infected flocks.