Abstract
Scrapie eradication efforts cost 18 million dollars annually in the United States and rely heavily upon PRNP genotyping of sheep. Genetic resistance might reduce goat scrapie and limit the risk of goats serving as a scrapie reservoir, so PRNP coding sequences were examined from 446 goats of 10 breeds, 8 of which had not been previously examined at PRNP. The 10 observed alleles were all related to one of two central haplotypes by a single amino acid substitution. At least five of these alleles (M142, R143, S146, H154, and K222) have been associated with increased incubation time or decreased odds of scrapie. To the best of our knowledge, neither S146 nor K222 has been found in any goats with scrapie, though further evaluation will be required to demonstrate true resistance. S146 was more common, present in several breeds at widely varying frequencies, while K222 was observed only in two dairy breeds at low frequency. Overall, this study provides frequency data on PRNP alleles in US goats, shows the pattern of relationships between haplotypes, and demonstrates segregation of multiple scrapieassociated alleles in several breeds not examined before at PRNP.
Highlights
Scrapie is a transmissible spongiform encephalopathy (TSE) that affects sheep and goats
Sheep have substitutions in amino acids 136, 154, and 171 with well-established allelic and genotypic effects on resistance to common scrapie strains [11]. This is consistent with genetic relationships to a wide variety of TSEs, including kuru and sporadic Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in elk and deer [3,12,13,14,18,19]
Several alleles have been associated with increased incubation time or decreased odds of scrapie, including those with amino acid substitutions M142, R143, S146, D146, H154, K222, and a 3-octapeptide repeat [1,5,8,9,20,24]
Summary
Scrapie is a transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Sheep have substitutions in amino acids 136, 154, and 171 with well-established allelic and genotypic effects on resistance to common scrapie strains [11] This is consistent with genetic relationships to a wide variety of TSEs, including kuru and sporadic Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in elk and deer [3,12,13,14,18,19]. Several alleles have been associated with increased incubation time or decreased odds of scrapie, including those with amino acid substitutions M142, R143, S146, D146, H154, K222, and a 3-octapeptide repeat [1,5,8,9,20,24] This suggests that a genetic approach to scrapie reduction in goats may have merit
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