Comparative mapping of the prion gene (PRNP) locus in cattle, sheep and man with PCR-generated probes

Prions are the unconventional causative agent of sub-acute transmissible spongiform encephalopathies in human and various mammals; for example, Scrapie of sheep, Bovine Spongiform Encephalopathy (BSE) of cattle, Cruetzfeldt-Jakob disease (CJD) and Fatal Familial Insomnia (FFI) of human (Prusiner 1994). These diseases are characterized by the accumulation in the brain tissue of a prion protein, PrPSc that is a partially proteinase-resistant isoform of the cellular protein, PrPc. Prions are the product of a single gene that is highly conserved in mammals. Hamster prion gene is composed of two exons; the entire coding region of the gene is contained within the second exon (Goldfarb et al. 1991). On the contrary, the genes of human, cattle, sheep, rat, and mouse have three exons, with the entire protein-coding region contained within exon 3 (Inoue et al. 1997). Cytogenetic analysis of the prion genes has been reported in human, where the gene has been localized on HSA 20p12-pter by a combination of somatic cell and in situ hybridization (Sparkes et al. 1986). In cattle, the gene has been mapped to syntenic group U11 (BTA 13) with a panel of bovine–rodent hybrid somatic cells (Ryan and Womack 1993; Hawkins et al. 1995) and has been recently incorporated into a radiation hybrid framework map of BTA 13 (Shla¨pfer et al. 1997). Here we report the direct localization of the PrP gene in cattle, sheep, and human by means of fluorescence in situ hybridization (FISH) with PCR-generated probes.