Transmissible Spongiform Encephalopaties (TSEs) are a group of neurodegenerative diseases caused by prions. All TSEs are characterised by an accumulation of an abnormal infectious form of the protein (PrP^Sc) in the brain. This protein is a pathogenic insoluble and partially proteinase‑resistant isoform of the cellular PrP (PrP^C), a copper binding protein. The pathogenic isoform is derived from the PrP^C by a postranslational process which probably only implies a change in the secondary structure of the protein, since the sequence of aminoacids of both proteins is the same. Prion protein is encoded by a highly conserved chromosomal gene named Prn‑p or PRNP. This gene contains two or three exons, depending on species, with a high degree of homology among them.
Several natural polymorphic variants of the PrP gene have been described as involved in resistance‑susceptibility to TSE. Such polymorphisms are either point mutations producing a change in the aminoacidic composition of the protein (single nucleotide polymorphisms (SNPs) or insertions and deletions affecting the number of octarepeats. There seems to be a direct relationship between the number of octarepeats and the susceptibility to the disease, the higher the number of octarepeats the more the susceptibility to disease. This type of variants, has been related to TSE in humans. In cattle, there is not evidence for an association between particular PrP gene polymorphisms and BSE although there are some indications (epidemiological, association studies and homology with other species) which also support the existence of a genetic basis. A few polymorphisms in the ORF of the PrP gene have been found, in cattle. They generally affect the number of octarepeats, combined with SNPs in these regions. In sheep, the resistance/susceptibility to scrapie, and possibly to BSE, is determined by polymorphisms in codons 136, 154 and 171 located in the ORF of the PrP gene. Homocygous animals for alleles ARR and AHQ are resistant to scrapie and those for alleles VRQ are susceptible. However, heterocygous show different degrees of susceptibility, in different breeds. Thus, in sheep, selection may become in a short period of time, a useful tool for prevention of TSE.