Nucleic Acids Research Advance Access originally published online on December 5, 2008
Nucleic Acids Research 2009 37(2):550-556; doi:10.1093/nar/gkn963
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2009, Vol. 37, No. 2 550-556
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Disease-specific motifs can be identified in circulating nucleic acids from live elk and cattle infected with transmissible spongiform encephalopathies
1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sun Center of Excellence for Visual Genomics, University of Calgary, Calgary, AB, Canada T2N 4N1, 2Chronix Biomedical GmbH, Goethealle 8, D-37073 Göttingen, 3Institute of Veterinary Medicine, Georg-August-Universität, Burckhardtweg 2, D-37077 Göttingen, Germany, 4Canadian Food Inspection Agency, Animal Diseases Research Institute, National and OIE BSE Reference Laboratories, Lethbridge, AB, Canada T1J 3Z4, 5Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, D-17439 Greifswald—Insel Riems, Germany and 6Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1
*To whom correspondence should be addressed. Tel: +1 403 220 4301; Fax: +1 403 210 9538; Email: csensen{at}ucalgary.ca
Received August 19, 2008. Revised November 11, 2008. Accepted November 12, 2008.
To gain insight into the disease progression of transmissible spongiform encephalopathies (TSE), we searched for disease-specific patterns in circulating nucleic acids (CNA) in elk and cattle. In a 25-month time-course experiment, CNAs were isolated from blood samples of 24 elk (Cervus elaphus) orally challenged with chronic wasting disease (CWD) infectious material. In a separate experiment, blood-sample CNAs from 29 experimental cattle (Bos taurus) 40 months post-inoculation with clinical bovine spongiform encephalopathy (BSE) were analyzed according to the same protocol. Next-generation sequencing provided broad elucidation of sample CNAs: we detected infection-specific sequences as early as 11 months in elk (i.e. at least 3 months before the appearance of the first clinical signs) and we established CNA patterns related to BSE in cattle at least 4 months prior to clinical signs. In elk, a progression of CNA sequence patterns was found to precede and correlate with macro-observable disease progression, including delayed CWD progression in elk with PrP genotype LM. Some of the patterns identified contain transcription-factor-binding sites linked to endogenous retroviral integration. These patterns suggest that retroviruses may be connected to the manifestation of TSEs. Our results may become useful for the early diagnosis of TSE in live elk and cattle.