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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.

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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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Competing interests

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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