NR AHAW
AU Laplanche,J.L.; Chatelain,J.C.; Westaway,D.; Thomas,S.; Dussaucy,M.; Brugere-Picoux,J.; Launay,J.M.
TI PrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis
QU Genomics 1993 Jan; 15(1): 30-7
PT journal article
AB Scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep and goats. An abnormal protease-resistant form of the host-encoded prion protein (PrP) accumulates in the brains of affected animals. As Sip, a gene controlling the incubation period of experimental and natural scrapie, is linked to the single-copy sheep PrP gene, we sought PrP coding sequence polymorphisms in flocks from the Romanov and Ile-de-France breeds endemically affected with natural scrapie. DNA samples from 153 sheep, including 29 natural scrapie cases, were screened by using polymerase chain reactions and denaturing gradient gel electrophoresis. Four predicted amino acid substitutions were found in the center of the PrP coding region: 112 Met -> Thr, 136 Ala -> Val, 154 Arg -> His, and 171 Gln -> Arg. These substitutions appeared mutually exclusive, defining five coding alleles. The 136Val allele, substituting a highly conserved Ala residue, in a homozygous or heterozygous state correlated with susceptibility to natural scrapie (chi 2 = 64.33, P < 0.001). This correlation indicates that the 136 Val allele may modulate development of the disease, implying a pivotal role for PrP molecules in natural scrapie, as has been observed for experimental scrapie and human prion diseases.
IN Schafe mit einer Mutation im Prionproteingen ersetzen an der Position 136 ein hochkonserviertes Alanin durch ein Valin und neigen zur Erkrankung an Scrapie.
MH Amino Acid Sequence; Animal; Base Sequence; Codon; DNA; Electrophoresis, Polyacrylamide Gel; Genotype; Membrane Glycoproteins/*genetics; Molecular Sequence Data; Polymerase Chain Reaction; *Polymorphism (Genetics); PrPsc Proteins; Prions/*genetics; Scrapie/*genetics; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.
AD FRA C. Bernard Neurochimie des Communications Cellulaires, Hopital Saint-Louis, Paris, France.
SP englisch
PO USA