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Direct selection of human genomic loci by microarray hybridization

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Abstract

We applied high-density microarrays to the enrichment of specific sequences from the human genome for high-throughput sequencing. After capture of 6,726 approximately 500-base 'exon' segments, and of 'locus-specific' regions ranging in size from 200 kb to 5 Mb, followed by sequencing on a 454 Life Sciences FLX sequencer, most sequence reads represented selection targets. These direct selection methods supersede multiplex PCR for the large-scale analysis of genomic regions.

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Figure 1: Schematic of the microarray direct genomic selection scheme.
Figure 2: Captured sequences.
Figure 3: Sequence coverage depth.

Change history

  • 21 October 2007

    In the version of this article initially published online, e-mail address of the corresponding author was incorrect. The correct address should be talbert@nimblegen.com. The error has been corrected for all versions of the article.

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Acknowledgements

We thank M. Zwick and D. Okou for helpful conversations, and the US National Human Genome Research Institute (grant U54 HG003273) and the US National Cancer Institute (grant R21HG004553) for support for this effort.

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Authors and Affiliations

Authors

Contributions

T.J.A., G.M.W. and R.A.G., experimental design, analysis and interpretation; M.N.M. and T.A.R., experimental design and data analysis; D.M.M. and L.N., sequencing; D.W. and X.S., data analysis; C.M.M. and C.J.P., laboratory experimentation (arrays); M.J.R., experimental design and laboratory experimentation (arrays).

Corresponding authors

Correspondence to Thomas J Albert or Richard A Gibbs.

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Competing interests

T.J.A., M.N.M, T.A.R., C.M.M., M.J.R. and C.J.P are employed by NimbleGen Systems.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1–3, Supplementary Methods (PDF 146 kb)

Supplementary Table 4

Exon target regions. (XLS 398 kb)

Supplementary Data 1

Selection microarray probe Sequences. (ZIP 57089 kb)

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Albert, T., Molla, M., Muzny, D. et al. Direct selection of human genomic loci by microarray hybridization. Nat Methods 4, 903–905 (2007). https://doi.org/10.1038/nmeth1111

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  • DOI: https://doi.org/10.1038/nmeth1111

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