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Selective enrichment of damaged DNA molecules for ancient genome sequencing
Open accessAbstract
Contamination by present-day human and microbial DNA is one of the major hindrances for large-scale genomic studies using ancient biological material. We describe a new molecular method, U selection, which exploits one of the most distinctive features of ancient DNA—the presence of deoxyuracils—for selective enrichment of endogenous DNA against a complex background of contamination during DNA library preparation. By applying the method to Neanderthal DNA extracts that are heavily contaminated with present-day human DNA, we show that the fraction of useful sequence information increases ∼10-fold and that the resulting sequences are more efficiently depleted of human contamination than when using purely computational approaches. Furthermore, we show that U selection can lead to a four- to fivefold increase in the proportion of endogenous DNA sequences relative to those of microbial contaminants in some samples. U selection may thus help to lower the costs for ancient genome sequencing of nonhuman samples also.
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Single-stranded preparation enables molecular selection of DNA templates carrying post-mortem DNA damage, increasing fraction of endogenous DNA and reducing downstream sequencing costs.
“Another advantage of the single-stranded preparation method is that it enables the molecular selection of DNA templates carrying evidence of post-mortem DNA damage, which can increase the fraction of endogenous DNA incorporated into sequencing libraries, and thus reduce downstream sequencing costs 43 .”
From Ancient DNA analysis (2021) · cites this paper as [43]
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Metadata
- Authors
- Gansauge, M.-T., & Meyer, M.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- Corresponding author
- Gansauge, Marie-Theres
- Meyer, Matthias
- ORCID
- Meyer, Matthias
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-07-31
- Volume
- 24
- Issue
- 9
- Pages
- 1543-1549
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC4158764
- OpenAlex
- W7095237570
- Cited by
- 118
- References
- 15
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 17 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 18 · 2015: 12 · 2014: 3
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Max-Planck-Gesellschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Keywords
- ancient DNA, DNA contamination, Neanderthal DNA, human contamination, microbial contamination, DNA library preparation
- MeSH terms
- Animals, Base Sequence, Deoxyuracil Nucleotides, Humans, Molecular Sequence Data, Sensitivity and Specificity, Genome, Sequence Analysis, DNA, DNA Contamination, Neanderthals
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