Novel single nucleotide polymorphisms in the specific protein 1 binding site of the bovine PRNP promoter in Japanese Black cattle: impairment of its promoter activity.
Intervirology
; 50(3): 190-6, 2007.
Article
em En
| MEDLINE
| ID: mdl-17283444
ABSTRACT
Susceptibility to transmissible spongiform encephalopathy and different alleles of the prion protein gene (PRNP) of humans and sheep are associated. A tentative association between PRNP promoter polymorphisms and bovine spongiform encephalopathy (BSE) susceptibility has been reported in German cattle, whereas none of the known polymorphisms within the bovine PRNP-coding sequence affect BSE susceptibility. In the present study, novel single nucleotide polymorphisms located in the 5'-flanking region of bovine PRNP affecting its expression were demonstrated in Japanese Black cattle. We sequenced exon 1, and the approximately 200-bp 5'-flanking region of the PRNP translation initiation site containing the proximal promoter of PRNP was harvested. We identified 7 single nucleotide polymorphisms -184A-->G, -141T-->C, -85T-->G, -47C-->A, -6C-->T, +17C-->T and +43C-->T. Six segregated haplotypes in the population were cloned into luciferase-expressing plasmids, transfected into N2a cells, and their reporter activities were measured 48 h after transfection. Six haplotypes showed a decreased expression level including -6C-->T in specific protein 1 binding site (p < 0.05) or -141T-->C (p < 0.01) at 48 h compared with the wild-type haplotype. These results advocate that certain polymorphisms such as specific protein 1 binding site polymorphisms in the bovine PRNP promoter region in Japanese Black cattle could influence promoter activity, suggesting that breeding cattle with such substitutions may be a useful approach in reducing BSE risk.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Príons
/
Regiões Promotoras Genéticas
/
Encefalopatia Espongiforme Bovina
/
Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
Limite:
Animals
Idioma:
En
Revista:
Intervirology
Ano de publicação:
2007
Tipo de documento:
Article