For this reason, we are currently working on increasing the number of PrP variants for analysis, including polymorphic variants described in some species that are, in addition, partially related to prion disease susceptibility data in vivo; and ad hoc designed artificial PrP variants (point mutants, indel mutants, chimeric constructs) specifically aimed to address if there is some critical position or domain determining spontaneous misfolding capacity regardless of neighboring or even distant regions. The gene discussed is PRNP; the disease is prion disease.