PrP gene polymorphisms in Cyprus goats and their association with resistance or susceptibility to natural scrapie

Genetic Resistance to Scrapie Infection in Experimentally Challenged Goats

“…Case-control studies of classical scrapie-affected herds (13)(14)(15)(16)(17)(18) and limited data from experimental challenges (intracerebral routes) (19,27) support the view that PrP K 222 allele goats might be strongly resistant to classical scrapie infection. Rare cases of the disease (n ϭ 3) were reported for heterozygous K 222 goats belonging to one single flock that displayed a high disease prevalence (27.4%), and no case has been reported so far for homozygous K 222 animals (14,21).…”

“…In goats, several field studies have identified coding mutations of the PRNP gene that are associated with a lower risk of developing classical scrapie, namely, the I/M 142 , N/D 146 and S 146 , R/Q 211 , and Q/K 222 alleles (13)(14)(15)(16)(17)(18). However, the low frequencies of these alleles in the goat population limit the possibility of reaching an unequivocal conclusion about the resistance/susceptibility to infection associated with these different PRNP genotypes (2,13,18).…”

PRNP variants in goats reduce sensitivity of detection of PrPSc by immunoassay

“…Such alterations include DNA encoding isoleucine (I) to methionine (M) at codon 142 (I142M), 4,13 histidine (H) to arginine (R) at codon 143 (H143R), 6 asparagine (N) to serine (S) or aspartic acid (D) at codon 146 (N146S or N146D), R to H at codon 154 (R154H), R to glutamine (Q) at codon 211 (R211Q), and Q to lysine (K) at codon 222 (Q222K). 22 To date, there have been limited observations of scrapie-positive goats that are N146S or N146D 30 or when at least 1 allele encodes K at codon 222. 1,7,22,38 A 2012 study demonstrated that allelic variation at codon 222 of the normal cellular prion protein (PrP C ) in goats decreases epitope recognition by mAb F99/97.6.1.…”

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells

“…These variants include Met-142, 13,17,21,23 His-154, 14,18,19,21,23 Arg-143, 18 and alleles with stronger protective effects, such as Ser-146, Asp-146, 14,19,20 Gln-211 11,21,23 and Lys-222. 11,[21][22][23] These alleles' relative low occurrence frequency among herds and/or goat breeds examined in field studies, suggests that additional investigations within the context of a well defined experimental scheme, including sufficient test samples and controls, are required prior to gaining further conclusive information on their effects.…”

“…6,[9][10][11][12][13][14][15][16] Field studies, conducted in different countries on a variety of goat breeds, assigned some degree of protection against scrapie to the following alleles Met-142, Arg-143, Asp-146, Ser-146, His-154, Gln-211 and Lys-222. 11,13,14,[17][18][19][20][21][22][23] Among these, Met-142 is linked to prolonged incubation period, 13,17,21,23 while Arg-143 18 and His-154 14,18,19,21,23 are associated with moderate protection. Ser-146 or Asp-146, 14,19,20 Gln-211 11,21,23 and Lys-222 11,[21][22][23] are associated with higher degrees of protection, suggesting that they could be used as candidate alleles, targeted by a potential selective breeding strategy.…”