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Microarray-based genomic selection for high-throughput resequencing

Abstract

We developed a general method, microarray-based genomic selection (MGS), capable of selecting and enriching targeted sequences from complex eukaryotic genomes without the repeat blocking steps necessary for bacterial artificial chromosome (BAC)-based genomic selection. We demonstrate that large human genomic regions, on the order of hundreds of kilobases, can be enriched and resequenced with resequencing arrays. MGS, when combined with a next-generation resequencing technology, can enable large-scale resequencing in single-investigator laboratories.

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Figure 1: Microarray-based genomic selection and resequencing of complex genomes.
Figure 2: Genomic regions (50 kb, 304 kb) resequenced in the two MGS validation experiments.

References

  1. Cutler, D.J. et al. Genome Res. 11, 1913–1925 (2001).

    CAS  Article  Google Scholar 

  2. Margulies, M. et al. Nature 437, 376–380 (2005).

    CAS  Article  Google Scholar 

  3. Shendure, J., Mitra, R.D., Varma, C. & Church, G.M. Nat. Rev. Genet. 5, 335–344 (2004).

    CAS  Article  Google Scholar 

  4. Shendure, J. et al. Science 309, 1728–1732 (2005).

    CAS  Article  Google Scholar 

  5. Zwick, M.E. et al. Genome Biol. 6, R10 (2005).

    Article  Google Scholar 

  6. Hinds, D.A. et al. Science 307, 1072–1079 (2005).

    CAS  Article  Google Scholar 

  7. Sjoblom, T. et al. Science 314, 268–274 (2006).

    Article  Google Scholar 

  8. Raymond, C.K. et al. Genomics 86, 759–766 (2005).

    CAS  Article  Google Scholar 

  9. Raymond, C.K., Sims, E.H. & Olson, M.V. Genome Res. 12, 190–197 (2002).

    CAS  Article  Google Scholar 

  10. Kouprina, N., Noskov, V.N. & Larionov, V. Methods Mol. Biol. 349, 85–101 (2006).

    CAS  PubMed  Google Scholar 

  11. Dahl, F. et al. Proc. Natl. Acad. Sci. USA 104, 9387–9392 (2007).

    CAS  Article  Google Scholar 

  12. Bashiardes, S. et al. Nat. Methods 2, 63–69 (2005).

    CAS  Article  Google Scholar 

  13. De Boulle, K. et al. Nat. Genet. 3, 31–35 (1993).

    CAS  Article  Google Scholar 

  14. Gu, Y., Lugenbeel, K.A., Vockley, J.G., Grody, W.W. & Nelson, D.L. Hum. Mol. Genet. 3, 1705–1706 (1994).

    CAS  Article  Google Scholar 

  15. Porreca, G.J. et al. Nat. Methods, advance online publication 14 October 2007 (doi:10.1038/nmeth1110).

    CAS  Article  Google Scholar 

  16. Albert, T.J. et al. Nat. Methods, advance online publication 14 October 2007 (doi:10.1038/nmeth1111).

    CAS  Article  Google Scholar 

  17. Bentley, D.R. Curr. Opin. Genet. Dev. 16, 545–552 (2006).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Funding for this work was provided by the US National Institutes of Health (NIH) National Institute of Mental Health RO1 MH076439-03 (MEZ) and by the Gift Fund, NIH.

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Correspondence to Michael E Zwick.

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T.J.A. and C.M. are employees of NimbleGen Systems, Inc.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–2, Supplementary Methods, Supplementary Table 1 (PDF 1776 kb)

Supplementary Data 1

Oligonucleotide Capture Probes for 50kb FMR1 Genomic Region (DOC 25359 kb)

Supplementary Data 2

Oligonucleotide Capture Probes for 304kb FMR1/FMR2 Genomic Region (DOC 28891 kb)

Supplementary Data 3

DNA Sequence Data for 50kb Region (ZIP 65 kb)

Supplementary Data 4

DNA Sequence Data for 304kb Region (ZIP 1893 kb)

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Okou, D., Steinberg, K., Middle, C. et al. Microarray-based genomic selection for high-throughput resequencing. Nat Methods 4, 907–909 (2007). https://doi.org/10.1038/nmeth1109

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  • DOI: https://doi.org/10.1038/nmeth1109

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