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This association suggests that the 129 genotype favours the selection of a distinct strain that in turn determines the phenotype. However, this mechanism cannot play a role in the phenotype determination of sporadic fatal insomnia (sFI) and a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) identified as sCJDMM2, which share 129 MM genotype and PrP<jats:sup>Sc<\/jats:sup> type 2 but are associated with quite distinct phenotypes. Our detailed comparative study of the PrP<jats:sup>Sc<\/jats:sup> conformers has revealed major differences between the two diseases, which preferentially involve the PrP<jats:sup>Sc<\/jats:sup> component that is sensitive to digestion with proteases (senPrP<jats:sup>Sc<\/jats:sup>) and to a lesser extent the resistant component (resPrP<jats:sup>Sc<\/jats:sup>). We conclude that these variations are consistent with two distinct strains in sFI and sCJDMM2, and that the rarer sFI is the result of a variant strain selection pathway that might be favoured by a different brain site of initial PrP<jats:sup>Sc<\/jats:sup> formation in the two diseases.<\/jats:p>","DOI":"10.1038\/srep38280","type":"journal-article","created":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T10:37:09Z","timestamp":1484563029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type"],"prefix":"10.1038","volume":"7","author":[{"given":"Laura","family":"Cracco","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio","family":"Notari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignazio","family":"Cali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man-Sun","family":"Sy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu G.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark L.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardino","family":"Ghetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian S.","family":"Appleby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Quan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byron","family":"Caughey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri G.","family":"Safar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Gambetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,1,16]]},"reference":[{"key":"BFsrep38280_CR1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1126\/science.6801762","volume":"216","author":"SB Prusiner","year":"1982","unstructured":"Prusiner, S. 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