Skip Navigation



Nucleic Acids Research Advance Access published online on August 22, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm588
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (171K) Freely available
Right arrow Screen PDF (192K) Freely available
Right arrow Supplementary Material
Right arrow Supplementary Material
Right arrowOA All Versions of this Article:
35/17/5717    most recent
gkm588v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Brotherton, P.
Right arrow Articles by Cooper, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brotherton, P.
Right arrow Articles by Cooper, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 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

Novel high-resolution characterization of ancient DNA reveals C > U-type base modification events as the sole cause of post mortem miscoding lesions

Paul Brotherton1,2,*, Phillip Endicott2, Juan J. Sanchez3, Mark Beaumont4, Ross Barnett5, Jeremy Austin1 and Alan Cooper1

1Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, Adelaide, SA 5005, Australia, 2Henry Wellcome Ancient Biomolecules Centre, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK, 3National Institute of Toxicology and Forensic Science, Canary Islands delegation, Tenerife, Spain, 4School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AG, UK and 5Department of Archaeology, University of Durham, South Road, Durham DH1 3L, UK

*To whom correspondence should be addressed. Tel: +44 1457 858605 Email: paul.brotherton{at}virgin.net

Received February 25, 2007. Revised July 16, 2007. Accepted July 17, 2007.

Ancient DNA (aDNA) research has long depended on the power of PCR to amplify trace amounts of surviving genetic material from preserved specimens. While PCR permits specific loci to be targeted and amplified, in many ways it can be intrinsically unsuited to damaged and degraded aDNA templates. PCR amplification of aDNA can produce highly-skewed distributions with significant contributions from miscoding lesion damage and non-authentic sequence artefacts. As traditional PCR-based approaches have been unable to fully resolve the molecular nature of aDNA damage over many years, we have developed a novel single primer extension (SPEX)-based approach to generate more accurate sequence information. SPEX targets selected template strands at defined loci and can generate a quantifiable redundancy of coverage; providing new insights into the molecular nature of aDNA damage and fragmentation. SPEX sequence data reveals inherent limitations in both traditional and metagenomic PCR-based approaches to aDNA, which can make current damage analyses and correct genotyping of ancient specimens problematic. In contrast to previous aDNA studies, SPEX provides strong quantitative evidence that C > U-type base modifications are the sole cause of authentic endogenous damage-derived miscoding lesions. This new approach could allow ancient specimens to be genotyped with unprecedented accuracy.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
A. W. Briggs, U. Stenzel, P. L. F. Johnson, R. E. Green, J. Kelso, K. Prufer, M. Meyer, J. Krause, M. T. Ronan, M. Lachmann, et al.
Patterns of damage in genomic DNA sequences from a Neandertal
PNAS, September 11, 2007; 104(37): 14616 - 14621.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.