GeneSet Information

Tier II GS129170 • prion disease incubation time 2 (Prdt2 Published QTL Chr 2)


QTL associated with prion disease incubation time 2. The confidence interval is Chr2:121731402-181608066 bp,+strand


QTL-Prdt2-Mouse-Chr 2









Lloyd SE, Onwuazor ON, Beck JA, Mallinson G, Farrall M, Targonski P, Collinge J, Fisher EM


Identification of multiple quantitative trait loci linked to prion disease incubation period in mice.


Proceedings of the National Academy of Sciences of the United States of America May 2001, Vol 98, pp. 6279-83


Polymorphisms in the prion protein gene are known to affect prion disease incubation times and susceptibility in humans and mice. However, studies with inbred lines of mice show that large differences in incubation times occur even with the same amino acid sequence of the prion protein, suggesting that other genes may contribute to the observed variation. 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-Jakob disease epidemic size utilizing existing epidemiological models. PUBMED: 11353827
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Annotation Information

Alleles (D000483)
Animals (D000818)
Encephalopathy, Bovine Spongiform (D016643)
Genome, Human (D015894)
Creutzfeldt-Jakob Syndrome (D007562)
Chromosomes (D002875)
Comprehension (D032882)
Quantitative Trait Loci (D040641)
Epidemics (D058872)
Scrapie (D012608)
Infection (D007239)
Amino Acid Sequence (D000595)
Identification (Psychology) (D007062)
Prion Diseases (D017096)
Confidence Intervals (D016001)
spongiform encephalopathy (MP:0002654)
pathogenesis (GO:0009405)

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