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A clone encoding PrP 27-30, the major protein in purifled preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein. Southern blotting with PrP cDNA revealed a single gene with the same restriction patterns in normal and scrapie-Infected brain DNA. A single PrP-related gene was also detected In murine and human DNA. PrP-related mRNA was found at similar levels in normal and scrap&infected hamster brain, as well as in many other normal tissues. Using antisera against PrP 27-30, a PrP-related protein was detected in crude extracts of infected brain and to a lesser extent in extracts of normal brain. Proteinase K digestion yielded PrP 27-30 in infected brain extract, but completely degraded the PrP-related protein in normal brain extract. No PrPrelated nucleic acids were found In purlfied preparations of …