Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

Abstract

Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc). This isoform presents an altered conformation that leads to aggregation in the host's central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be influenced by specific genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal's genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171). The most variable codon was 171, where all described alleles were identified. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons, all of them corresponding to the wild-type prion protein. Regarding the risk degree of developing scrapie, most of the animals (96%) had genotypes corresponding to risk groups 1 to 3 (very low to moderate), with only 4% in the higher risks group. Our data is discussed in relation to preventive measures involving genotyping and positive selection to control the disease.

Seleção de ovinos geneticamente resistentes ao scrapie

“…Mais de 26 polimorfismos foram confirmados por pesquisadores e outros ainda não foram caracterizados (GOLDMANN et al, 1990;LAPLANCHE et al, 1993;BELT et al, 1995;BOSSERS et al, 1996;THORGEIRSDOTTIR et al, 1999;O'ROURKE et al, 1996;DeSILVA et al, 2003;GUO et al, 2003;BILLINIS et al, 2004;HEATON et al, 2010;ANDRADE et al, 2011). A importância relativa destes polimorfismos sobre a resistência ou susceptibilidade ao scrapie ainda está por ser definida.…”

“…Por exemplo, o alelo ARQ é considerado altamente susceptível às EET em geral (inclusive à infecção experimental por EEB); porém, em um isolado em particular, tipo SSBP-1, não se consegue propagá-lo em animais ARQ/ARQ (GOLDMANN et al, 1994 (O´ROURKE et al, 1996;, França (ELSEN et al, 1999), Grã-Bretanha (HUNTER et al, 1997a;1997b;TONGUE et al, 2004;EGLIN et al, 2005) No Brasil, ainda são poucos os trabalhos de genotipagem das raças criadas no país (PASSOS et al, 2008;SOTOMAIOR et al, 2008;ANDRADE et al, 2011) e, principalmente, das raças nativas (LIMA et al, 2007;PACHECO et al, 2007). Ianella et al (2012), no estudo com maior número de genotipagens feitas no país até o momento, analisaram 1400 animais de 13 raças, incluindo várias raças brasileiras como Bergamácia, Crioula, Morada Nova, Rabo Largo, Santa Inês e Somalis Brasileiro.…”

“…Alguns trabalhos mostram que existem diferenças nas frequências genotípicas do gene PRNP, quando comparados aos resultados de outros países (SOTOMAIOR, 2007), indicando a necessidade de se ampliar o número de animais genotipados antes que qualquer programa de controle do scrapie seja implantado no Brasil. É essencial, também, que se conheça a estrutura populacional e o grau de variabilidade genética do gene PRNP entre as diferentes raças, como tem sido demonstrado nos primeiros trabalhos brasileiros sobre genotipagem de ovinos (LIMA et al, 2007;PACHECO et al, 2007;PASSOS et al, 2008;SOTOMAIOR et al 2008;ANDRADE et al, 2011;IANELLA et al, 2012).…”

Prion protein gene polymorphisms and accumulation of pathogenic prion protein (PrPSc) in a herd with previously confirmed scrapie cases

“…After this, other scrapie cases have been reported and published (http://www.oie.int; RIBEIRO et al, 2007;ANDRADE et al, 2011). Some of these cases were on the animals from Paraná State (SOTOMAIOR et al, 2012).…”

“…In Brazil, although there is not yet a breeding program to control scrapie, some data on PRNP polymorphisms have been published (LIMA et al, 2007;PACHECO et al, 2007;SOTOMAIOR et al, 2008;PASSOS et al, 2008;ANDRADE et al, 2011;IANELLA et al, 2012;SANTOS et al, 2012). These articles mainly give the percentages of the different polymorphisms, but do not make any kind of association with the presence of the PrP Sc .…”