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Genetic susceptibility to prion diseases

Genetic loci other than the prion protein gene have a major effect on prion disease incubation time in mice; multiple quantitative trait loci on three chromosomes can explain 82% of the variance.

Tudor Toma(ttoma@mail.dntis.ro)

Prion diseases such as variant Creutzfeldt–Jakob disease and scrapie have prolonged incubation periods due to unknown molecular mechanisms. Polymorphisms in the prion protein gene are known to affect incubation duration in humans and other animals. But large differences in incubation times still occur even with the same amino acid sequence of the prion protein, suggesting that other genes are also involved. In May 22 Proceedings of the National Academy of Sciences Sarah Lloyd and colleagues from Imperial College School of Medicine characterize the first genes that are implicated in susceptibility to prion diseases in mice.

Lloyd et al analyzed 1,009 mice from an F2 intercross between two strains — CASTyEi and NZWyOlaHSd — with significantly different incubation periods when infected with scrapie prions. Interval mapping identified three highly significantly linked regions on chromosomes 2, 11, and 12, which include multiple linked quantitative trait loci and can explain 82% of the...

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