Document Detail

Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie.
MedLine Citation:
PMID:  7897344     Owner:  NLM     Status:  MEDLINE    
Scrapie is a fatal neurodegenerative disease of sheep that belongs to the group of prion diseases found in humans and animals. The host encoded prion protein (PrP) plays a central role in the disease process. In the PrP genes of man, mice and sheep, polymorphisms have been found that are associated with disease susceptibility and pathogenesis. We have used denaturing gradient gel electrophoresis (DGGE) to detect polymorphisms in the sheep PrP gene. In addition to the already described polymorphisms at codons 136, 154 and 171, we identified a hitherto unknown G --> T transition at codon 171. This transition is responsible for a glutamine to histidine substitution. An arginine to glutamine substitution at this position has been described previously. DGGE allowed us to identify five different combinations of these polymorphisms within the PrP gene representing five allelic variants, which were cloned and sequenced. Based on the triplet sequences present at codons 136, 154 and 171 these allelic variants were designated PrPVRQ, PrPARR, PrPARQ, PrPARH and PrPAHQ. To determine the association of these allelic variants with natural scrapie, we screened 34 scrapie affected and 91 healthy control sheep of the Texel breed for the presence of these allelic variants. In these two groups, the five variants gave rise to 13 different genotypes. The distribution of the allelic variants among both groups showed marked differences. The PrPVRQ variant was present with high frequency in scrapie affected sheep, whereas the PrPARR variant was almost exclusively present in the healthy group. Two other variants, PrPARQ and PrPARH, were found in both groups with equal frequencies. The data obtained suggest modulation of disease susceptibility in these Texel sheep by at least five different PrP allelic variants, with the PrPVRQ and PrPARR alleles acting in a dominant, but opposite fashion over the PrPARQ and PrPARH alleles. The frequency of the PrPAHQ variant was too low to draw any conclusions.
P B Belt; I H Muileman; B E Schreuder; J Bos-de Ruijter; A L Gielkens; M A Smits
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of general virology     Volume:  76 ( Pt 3)     ISSN:  0022-1317     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-04-27     Completed Date:  1995-04-27     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  509-17     Citation Subset:  IM    
Department of Molecular Biology, DLO-Institute for Animal Science and Health (ID-DLO), Lelystad, The Netherlands.
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MeSH Terms
Base Sequence
Cloning, Molecular
Codon / genetics
DNA Mutational Analysis
Electrophoresis, Polyacrylamide Gel / methods
Genetic Markers
Molecular Sequence Data
Nucleic Acid Denaturation
Point Mutation / genetics
Polymorphism, Genetic*
Prions / genetics*
Scrapie / genetics*
Reg. No./Substance:
0/Codon; 0/Genetic Markers; 0/Prions

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