Simultaneous genotyping, gene-expression measurement, and detection of allele-specific expression with oligonucleotide arrays

  1. James Ronald1,2,
  2. Joshua M. Akey1,2,
  3. Jacqueline Whittle2,3,
  4. Erin N. Smith2,
  5. Gael Yvert2,4, and
  6. Leonid Kruglyak1,2,3,5
  1. 1 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
  2. 2 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
  3. 3 Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

Abstract

Oligonucleotide microarrays provide a high-throughput method for exploring genomes. In addition to their utility for gene-expression analysis, oligonucleotide-expression arrays have also been used to perform genotyping on genomic DNA. Here, we show that in segregants from a cross between two unrelated strains of Saccharomyces cerevisiae, high-quality genotype data can also be obtained when mRNA is hybridized to an oligonucleotide-expression array. We were able to identify and genotype nearly 1000 polymorphisms at an error rate close to 3% in segregants and at an error rate of 7% in diploid strains, a performance comparable to methods using genomic DNA. In addition, we demonstrate how simultaneous genotyping and gene-expression profiling can reveal cis-regulatory variation by screening hundreds of genes for allele-specific expression. With this method, we discovered 70 ORFs with evidence for preferential expression of one allele in a diploid hybrid of two S. cerevisiae strains.

Footnotes

  • [Supplemental material is available online at www.genome.org.]

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2850605.

  • 4 Present address: Centre G. Durand, UMR-CNRS 5504, 31077 Toulouse cedex 04, France.

  • 5 Corresponding author. E-mail leonid{at}fhcrc.org; fax (206) 667-2383.

    • Accepted November 16, 2004.
    • Received June 4, 2004.
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