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Updated: May 13, 2026
12:57
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Genetics of prion diseases
Sarah E Lloyd1, Simon Mead, John Collinge
1MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK.
Current Opinion in Genetics & Development
|March 23, 2013
Summary
Genetic factors beyond the prion protein gene influence prion disease susceptibility. New gene loci identified in human and mouse studies offer novel insights into these fatal neurodegenerative conditions.
Area of Science:
- Neurogenetics
- Molecular Biology
- Disease Mechanisms
Background:
- Prion diseases are fatal, transmissible neurodegenerative disorders affecting humans and animals.
- The prion protein gene (PRNP) is a primary determinant of susceptibility.
- Emerging evidence indicates additional genetic factors play a significant role.
Purpose of the Study:
- To identify novel genetic modifiers of prion disease susceptibility.
- To explore the genetic architecture of prion diseases beyond the PRNP gene.
Main Methods:
- Genome-wide association studies (GWAS) in human Creutzfeldt-Jakob disease (CJD) cases.
- Complex genetic crosses in mouse models.
- Expression profiling analysis.
Main Results:
- Identified four new human loci associated with CJD: ZBTB38-RASA2, MTMR7, and NPAS2.
- Discovered new mouse modifiers including Cpne8, and confirmed Rarb and Stmn2.
- Expression profiling revealed Hspa13 as a candidate, reducing incubation time in transgenic models.
Conclusions:
- Multiple genes, in addition to PRNP, contribute to prion disease susceptibility.
- These newly identified genes represent potential therapeutic targets.
- Further research into these genetic factors will advance understanding of prion disease pathogenesis.
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