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Plos Genetics : Hectd2is Associated with Susceptibility to Mouse and Human Prion Disease, Volume 5

By Carlson, George A.

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Book Id: WPLBN0003927774
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Hectd2is Associated with Susceptibility to Mouse and Human Prion Disease, Volume 5  
Author: Carlson, George A.
Volume: Volume 5
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Historic
Publication Date:
Publisher: Plos

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Carlson, G. A. (n.d.). Plos Genetics : Hectd2is Associated with Susceptibility to Mouse and Human Prion Disease, Volume 5. Retrieved from http://worldlibrary.org/


Description
Description : Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods.

 

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