RESUMO
The genetics of the prion protein gene (PRNP) play a crucial role in determining the relative susceptibility to transmissible spongiform encephalopathies (TSEs) in several mammalian species. To determine the PRNP gene variability in European red deer (Cervus elaphus), roe deer (Capreolus capreolus) and chamois (Rupicapra rupicapra), the PRNP open reading frame from 715 samples was analysed to reveal a total of ten single nucleotide polymorphisms (SNPs). In red deer, SNPs were found in codons 15, 21, 59, 78, 79, 98, 136, 168 and 226. These polymorphisms give rise to 12 haplotypes, and one of which is identical to the PRNP of American wapiti (Rocky Mountain elk, Cervus elaphus nelsoni). One silent mutation at codon 119 was detected in chamois and no SNPs were found in roe deer. This analysis confirmed that European wild ruminants have a PRNP genetic background that is compatible with TSE susceptibility, including chronic wasting disease.
Assuntos
Cervos/genética , Doenças Priônicas/genética , Príons/genética , Animais , Sequência de Bases , DNA/química , DNA/genética , Predisposição Genética para Doença , Variação Genética , Haplótipos , Itália , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Nucleotídeo Único , Escócia , Análise de Sequência de DNARESUMO
Variation in PrP prion gene sequence appears to modulate susceptibility to chronic wasting disease (CWD), a naturally occurring prion disease affecting four North American species of the family Cervidae. Wapiti (Cervus elaphus nelsoni) PrP is polymorphic at codon 132 [methionine (M) or leucine (L)]. We genotyped 171 samples, collected between 2002 and 2005 from CWD-infected and uninfected wapiti from three free-ranging populations in Colorado, USA, to study influences of PrP polymorphisms on CWD susceptibility further. Overall genotype frequencies for 124 apparently uninfected animals were 65.3 % MM132, 32.3 % ML132 and 2.4 % LL132; for 47 CWD-infected animals, these frequencies were 70.2 % MM132, 27.7 % ML132 and 2.1 % LL132. Surprisingly, our data revealed that, among recent (approx. 2002--2005) CWD cases detected in free-ranging Colorado wapiti, the three PrP codon 132 genotypes were represented in proportion to their abundance in sampled populations (P> or =0.24) and all three genotypes showed equivalent susceptibility to infection.
Assuntos
Polimorfismo Genético , Príons/genética , Ruminantes , Doença de Emaciação Crônica/genética , Animais , Colorado , Suscetibilidade a Doenças , Genótipo , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
Susceptibility and incubation periods of transmissible spongiform encephalopathies, such as scrapie in sheep, are modulated by the PrP gene. The standard model of association between ovine PrP genetics and classical scrapie susceptibility is based on PrP genotypes with respect to codons 136, 154 and 171, e.g. alanine-arginine-glutamine (ARQ). It is demonstrated here that a proline to leucine substitution in codon 168 of the ovine PrP protein gene is associated with increased resistance to experimental bovine spongiform encephalopathy (BSE) inoculation. The ARL(168)Q PrP allele was found in heterozygous ARP(168)Q/ARL(168)Q sheep that have so far survived intravenous BSE challenge three times longer than BSE-challenged homozygous ARP(168)Q/ARP(168)Q sheep, which develop disease in around 700 days. In contrast, the L141F polymorphism does not appear to be associated with susceptibility to intravenous BSE challenge.
