Structure and Comparative Analysis of the Bovine Prion Gene Locus

S.      Comincini; B.      Castiglioni; I.      Del Vecchio; M.G.      Foti; L.      Ferretti

Abstract

Prion diseases are transmissible neurodegenerative disorders that affect a wide range of mammalian species. The prion protein gene, Prnp, modulates the incidence and incubation periods of the disease in sheep, goat, mouse and man. Because of the current absence of such a correlation in cattle, the bovine Prnp gene was investigated and its outline skeleton, i.e. the exon/intron structure was determined. The bovine prion gene was physically mapped on bovine chromosome 13 (BTA13q17) the comparative analysis showed a high level of conservation between cattle and other mammals. The bovine gene contains three exons the first is contiguous to the promoter and to the regulatory elements the second is transcriptionally active in most species, but does not contain coding information the last contains the entire coding region. Additional non-coding sequences, conserved among different species, were also identified, particularly in the 3 untranslated region. The neighbouring region of the prion gene in differ ent species was also examined in search of other genes that may shed light on the prion function. The prion-gene chromosomal region showed a remarkable density of coding sequences one of them, the prion-doppel, Prnd, has structural similarities with the prion gene itself. This finding, first reported in man and mouse, supports the existence of a Prion-family , as the experimental evidence in the mouse of chimaeric transcripts generated by intergenic splicing between the genes Prnp and Prnd would confirm.

Keywords: Comparative Analysis, Bovine Prion Gene Locus, Prion protein Gene, <, / kwd, >, Prnp Gene, Prion-doppel, Prnd, Prion-family, Creutzfeldt-Jacob disease CJD, INRTON 1