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Mining the human genome using microarrays of open reading frames

Nature Genetics volume 26, pages 315–318 (2000)Cite this article

Abstract

To test the hypothesis that the human genome project will uncover many genes not previously discovered by sequencing of expressed sequence tags (ESTs), we designed and produced a set of microarrays using probes based on open reading frames (ORFs) in 350 Mb of finished and draft human sequence. Our approach aims to identify all genes directly from genomic sequence by querying gene expression. We analysed genomic sequence with a suite of ORF prediction programs, selected approximately one ORF per gene, amplified the ORFs from genomic DNA and arrayed the amplicons onto treated glass slides. Of the first 10,000 arrayed ORFs, 31% are completely novel and 29% are similar, but not identical, to sequences in public databases. Approximately one-half of these are expressed in the tissues we queried by microarray. Subsequent verification by other techniques confirmed expression of several of the novel genes. Expressed sequence tags (ESTs) have yielded vast amounts of data1,2, but our results indicate that many genes in the human genome will only be found by genomic sequencing.

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Figure 1: Representation of clustering of expression.
Figure 2: A 'Mondrian' of a 'virtual' BAC.
Figure 3: A study of BAC AL049839, depicted by 'Mondrian'.

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Acknowledgements

We thank D. Jenkins and other members of the ART team for assistance, support and encouragement; R. Thomas for programming assistance; Operon for cooperation on this project; and J. Graham for the use of DiCTion.

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Author notes

  1. Sharron G. Penn and David R. Rank: These authors contributed equally to this work.

Authors and Affiliations

  1. Advanced Research Team, Molecular Dynamics Inc., Sunnyvale, California, USA

    Sharron G. Penn, David R. Rank & David K. Hanzel

  2. Illumina, Inc., San Diego, California, USA

    David L. Barker

Authors
  1. Sharron G. Penn
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  2. David R. Rank
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  3. David K. Hanzel
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  4. David L. Barker
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Correspondence to David R. Rank.

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Penn, S., Rank, D., Hanzel, D. et al. Mining the human genome using microarrays of open reading frames. Nat Genet 26, 315–318 (2000). https://doi.org/10.1038/81613

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