Pulling out the 1%: whole-Genome capture for the targeted enrichment of ancient dna sequencing libraries

Carpenter, Meredith L., Buenrostro, Jason D., Valdiosera, Cristina, Schroeder, Hannes, Allentoft, Morten E., Sikora, Martin, Rasmussen, Morten, Gravel, Simon, Guillen, Sonia, Nekhrizov, Georgi, Leshtakov, Krasimir, Dimitrova, Diana, Theodossiev, Nikola, Pettener, Davide, Luiselli, Donata, Sandoval, Karla, Moreno-Estrada, Andres, Li, Yingrui, Wang, Jun, Gilbert, M. Thomas P., Willerslev, Eske, Greenleaf, William J. and Bustamante, Carlos D. (2013) Pulling out the 1%: whole-Genome capture for the targeted enrichment of ancient dna sequencing libraries. American Journal of Human Genetics, 93 5: 852-864. doi:10.1016/j.ajhg.2013.10.002

Author Carpenter, Meredith L.
Buenrostro, Jason D.
Valdiosera, Cristina
Schroeder, Hannes
Allentoft, Morten E.
Sikora, Martin
Rasmussen, Morten
Gravel, Simon
Guillen, Sonia
Nekhrizov, Georgi
Leshtakov, Krasimir
Dimitrova, Diana
Theodossiev, Nikola
Pettener, Davide
Luiselli, Donata
Sandoval, Karla
Moreno-Estrada, Andres
Li, Yingrui
Wang, Jun
Gilbert, M. Thomas P.
Willerslev, Eske
Greenleaf, William J.
Bustamante, Carlos D.
Title Pulling out the 1%: whole-Genome capture for the targeted enrichment of ancient dna sequencing libraries
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2013-11-07
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2013.10.002
Open Access Status Not Open Access
Volume 93
Issue 5
Start page 852
End page 864
Total pages 13
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Abstract Most ancient specimens contain very low levels of endogenous DNA, precluding the shotgun sequencing of many interesting samples because of cost. Ancient DNA (aDNA) libraries often contain <1% endogenous DNA, with the majority of sequencing capacity taken up by environmental DNA. Here we present a capture-based method for enriching the endogenous component of aDNA sequencing libraries. By using biotinylated RNA baits transcribed from genomic DNA libraries, we are able to capture DNA fragments from across the human genome. We demonstrate this method on libraries created from four Iron Age and Bronze Age human teeth from Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries yielded an average of 1.2% of reads mapping to the human genome (including duplicates). After capture, this fraction increased substantially, with up to 59% of reads mapped to human and enrichment ranging from 6- to 159-fold. Furthermore, we maintained coverage of the majority of regions sequenced in the precapture library. Intersection with the 1000 Genomes Project reference panel yielded an average of 50,723 SNPs (range 3,062-147,243) for the postcapture libraries sequenced with 1 million reads, compared with 13,280 SNPs (range 217-73,266) for the precapture libraries, increasing resolution in population genetic analyses. Our whole-genome capture approach makes it less costly to sequence aDNA from specimens containing very low levels of endogenous DNA, enabling the analysis of larger numbers of samples.
Keyword Bacterial sepsis detection
Magnetic nanoparticles
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 90 times in Thomson Reuters Web of Science Article | Citations
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