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To identify these loci we analyzed 1,009 animals from an F2 intercross between two strains of mice, CAST\/Ei and NZW\/OlaHSd, with significantly different incubation periods when challenged with RML scrapie prions. Interval mapping identified three highly significantly linked regions on chromosomes 2, 11, and 12; composite interval mapping suggests that each of these regions includes multiple linked quantitative trait loci. Suggestive evidence for linkage was obtained on chromosomes 6 and 7. The sequence conservation between the mouse and human genome suggests that identification of mouse prion susceptibility alleles may have direct relevance to understanding human susceptibility to bovine spongiform encephalopathy (BSE) infection, as well as identifying key factors in the molecular pathways of prion pathogenesis. However, the demonstration of other major genetic effects on incubation period suggests the need for extreme caution in interpreting estimates of variant Creutzfeldt\u2013Jakob disease epidemic size utilizing existing epidemiological models.<\/jats:p>","DOI":"10.1073\/pnas.101130398","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"6279-6283","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":154,"title":["Identification of multiple quantitative trait loci linked to prion disease incubation period in mice"],"prefix":"10.1073","volume":"98","author":[{"given":"Sarah E.","family":"Lloyd","sequence":"first","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obia N.","family":"Onwuazor","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Beck","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Mallinson","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Farrall","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Targonski","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, United Kingdom; and Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M. 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