Functional relevance of DNA polymorphisms within the promoter region of the prion protein gene and their association to BSE infection

Kashkevich, Kseniya; Humeny, Andreas; Ziegler, Ute; Groschup, Martin H; Nicken, Petra; Leeb, Tosso; Fischer, Christine; Becker, Cord-Michael; Schiebel, Katrin (2007). Functional relevance of DNA polymorphisms within the promoter region of the prion protein gene and their association to BSE infection. FASEB journal, 21(7), pp. 1547-55. Bethesda, Md.: Federation of American Societies for Experimental Biology 10.1096/fj.06-7522com

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Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases that can occur spontaneously or can be caused by infection or mutations within the prion protein gene PRNP. Nonsynonymous DNA polymorphisms within the PRNP gene have been shown to influence susceptibility/resistance to infection in sheep and humans. Analysis of DNA polymorphisms within the core promoter region of the PRNP gene in four major German bovine breeds resulted in the identification of both SNPs and insertion/deletion (indel) polymorphisms. Comparative genotyping of both controls and animals that tested positive for bovine spongiform encephalopathy (BSE) revealed a significantly different distribution of two indel polymorphisms and two SNPs within Braunvieh animals, suggesting an association of these polymorphisms with BSE susceptibility. The functional relevance of these polymorphisms was analyzed using reporter gene constructs in neuronal cells. A specific haplotype near exon 1 was identified that exhibited a significantly lower expression level. Genotyping of nine polymorphisms within the promoter region and haplotype calculation revealed that the haplotype associated with the lowest expression level was underrepresented in the BSE group of all breeds compared to control animals, indicating a correlation of reduced PRNP expression and increased resistance to BSE.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics

UniBE Contributor:

Leeb, Tosso

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

21 Jan 2014 15:05

Publisher DOI:

10.1096/fj.06-7522com

PubMed ID:

17255470

Web of Science ID:

000246117000029

URI:

https://boris.unibe.ch/id/eprint/22149 (FactScience: 32044)

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