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A Statistical Approach to Identify Ancient Template DNA
Authors:Agnar Helgason  Snæbjörn Pálsson  Carles Lalueza-Fox  Shyamali Ghosh  Sigrún Sigurðardóttir  Adam Baker  Birgir Hrafnkelsson  Lilja Árnadóttir  Unnur Þorsteinsdóttir  Kári Stefánsson
Institution:(1) deCODE Genetics, Sturlugata 8, 101, Reykjavik, Iceland;(2) Department of Biology, University of Iceland, Reykjavik, Iceland;(3) Department of Biology, University of Barcelona, Barcelona, Spain;(4) Faculty of Engineering, University of Iceland, Reykjavik, Iceland;(5) National Museum of Iceland, Reykjavik, Iceland
Abstract:One of the key problems in the study of ancient DNA is that of authenticating sequences obtained from PCR amplifications of highly degraded samples. Contamination of ancient samples and postmortem damage to endogenous DNA templates are the major obstacles facing researchers in this task. In particular, the authentication of sequences obtained from ancient human remains is thought by many to be rather challenging. We propose a novel approach, based on the c statistic, that can be employed to help identify the sequence motif of an endogenous template, based on a sample of sequences that reflect the nucleotide composition of individual template molecules obtained from ancient tissues (such as cloned products from a PCR amplification). The c statistic exploits as information the most common form of postmortem damage observed among clone sequences in ancient DNA studies, namely, lesion-induced substitutions caused by cytosine deamination events. Analyses of simulated sets of templates with miscoding lesions and real sets of clone sequences from the literature indicate that the c-based approach is highly effective in identifying endogenous sequence motifs, even when they are not present among the sampled clones. The proposed approach is likely to be of general use to researchers working with DNA from ancient tissues, particularly from human remains, where authentication of results has been most challenging. Reviewing Editor: Dr. Magnus Nordborg]
Keywords:Ancient DNA  Authentication  Postmortem damage  Statistical method
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