Identification of prion protein gene polymorphisms in goats from Italian scrapie outbreaks

Abstract

Susceptibility to scrapie in sheep is influenced by polymorphisms of the prion protein (PrP) gene, whereas no strong association between genetics and scrapie has yet been determined in goats due to the limited number of studies on these animals. In this case-control study on 177 goats from six Italian scrapie outbreaks, the association between PrP alleles and the occurrence of scrapie was studied. Three silent mutations and 11 PrP polymorphisms were identified, of which two polymorphisms (L133Q and M137I) and one silent mutation (T202T) have not been reported previously. Twelve alleles were determined by cloning. Statistical analysis suggested a possible protective role against scrapie for the glutamine to lysine mutation at codon 222.

PrPgenetics in ruminant transmissible spongiform encephalopathies

“…A PrP variant with three repeats and an additional W102G polymorphism was also associated with longer incubation periods after experimental challenges [33]. Polymorphisms with some resistance (low risk) association to scrapie are H143R, N146S/D, R154H and Q222K [3,11,74,92] [5] implies that the mechanisms underlying the interactions between PrP and agent are the same in different species, therefore highlighting the fact that it ought to be possible to establish general rules for PrP genetics. We may therefore deduce for example that R143 in sheep will also have a low risk association.…”

“…Codon 177 (Asn or Thr) is in the neighbourhood of codon 171 which again is associated with scrapie. Codon 226 (Gln or Glu) is adjacent to codon 225, which has been associated with CWD susceptibility [53] and close to codon 222, which is proposed to enhance resistance to scrapie in goats [3,92]. It remains to be seen whether these differences can give some protection for the transmission of TSE between species.…”

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. Different experimental approaches, utilizing either in vitro 24 or in vivo [25][26][27][28] methodologies, have been used toward this direction.…”

“…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.…”

Prion gene (PRNP) haplotype variation in United States goat breeds(Open Access publication)

“…Although there is some evidence that goat genetics plays an important role in goat scrapie, no related management measure has been implemented. Several [1,5,8,20,27]. 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].…”