Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Massively parallel exon capture and library-free resequencing across 16 genomes

Nature Methods volume 6, pages 315–316 (2009)Cite this article

To the Editor: The adoption of molecular inversion probes (MIPs) to massively parallel exon capture1 has been limited by representational and allelic bias. We modified this protocol, enabling simultaneous amplification and accurate shotgun sequencing of 50,000 exons. We also tested the scalability and accuracy of direct sequencing of MIP amplicons, which circumvents all shotgun library construction, by resequencing 1 megabase of coding sequence across 16 human genomes with >99% HapMap sequence concordance.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Optimization yields reduced representational and allelic bias.
Figure 2: Schematic of MIP-based exon capture and direct resequencing.

References

  1. Porreca, G.J. et al. Nat. Methods 4, 931–936 (2007).

    Article  CAS  Google Scholar 

  2. Hardenbol, P. et al. Genome Res. 15, 269–275 (2005).

    Article  CAS  Google Scholar 

  3. Bentley, D.R. et al. Nature 456, 53–59 (2008).

    Article  CAS  Google Scholar 

  4. Li, H., Ruan, J. & Durbin, R. Genome Res. 18, 1851–1858 (2008).

    Article  CAS  Google Scholar 

  5. Shendure, J. & Ji, H. Nat. Biotechnol. 26, 1135–1145 (2008).

    Article  CAS  Google Scholar 

  6. Albert, T.J. et al. Nat. Methods 4, 903–905 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from the US National Institutes of Health (NIH) National Heart Lung and Blood Institute (R01 HL094976 to D.A.N. and J.S.) and the NIH National Human Genome Research Institute (R21 HG004749 to J.S.). E.H.T. is supported by a training fellowship from the NIH National Human Genome Research Institute (T32 HG00035). S.B.N. is supported by the Agency for Science, Technology and Research, Singapore. We thank K. Bertucci and S. da Ponte for technical assistance with sequencing; J. Smith, G. Cooper and I. Stanway for assistance with genotyping data; H. Ji, J. Li, K. Zhang, G. Church, J. Teer, J. Egertson, R. Lifton and G. Porreca for helpful discussions; and E. Leproust and W. Woo for supplying oligo libraries.

Author information

Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, Seattle, Washington, USA

    Emily H Turner, Choli Lee, Sarah B Ng, Deborah A Nickerson & Jay Shendure

Authors
  1. Emily H Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Choli Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah B Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deborah A Nickerson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jay Shendure
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jay Shendure.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Tables 1–2, Supplementary Note 1, Supplementary Methods (PDF 123 kb)

Supplementary Data 1

Design and targets for 13,000 MIP precursor oligos (TXT 1641 kb)

Supplementary Data 2

Variants called for 16 HapMap individuals targeted with 13,000-plex MIP capture (TXT 512 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Turner, E., Lee, C., Ng, S. et al. Massively parallel exon capture and library-free resequencing across 16 genomes. Nat Methods 6, 315–316 (2009). https://doi.org/10.1038/nmeth.f.248

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.f.248

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing