There is a genetic component associated with several of the human TSE diseases. A specific point mutation at codon 178 is associated with fatal familial insomnia. Point mutations at codons 102, 105, 117, 145, 198, and 217 are associated with GSS syndrome. Point mutations at codons 178, 180, 200, 210, and 232 are associated with CJD. Various insertions into the octapeptide repeat region of the PrP gene have also been associated with human TSE's. It appears that the methionine/valine polymorphism at codon 129 may modify the phenotype and the transmission rate from GSS syndrome patients to mice. No abnormalities in the sequence of the PrP gene in kuru patients were found.

There is also a genetic component associated with sheep scrapie. Point mutations at codon 171 of the sheep PrP gene are linked to the disease in the Corriedale, Lacaune, Romanov, Suffolk, and Texel breeds.An analysis of 370 cattle from Scotland revealed no difference between healthy cattle and cattle with BSE in the number of octapeptide repeat sequences (either five or six) and in a silent HindII restriction site polymorphism on the PrP gene. No data were found that compared the sequence of the PrP gene of healthy deer, elk, mink, and goats with those afflicted by TSE's.