Methods

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

    • 1 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    • 2 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    • 3 Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
Published February 1, 2005. Vol 15 Issue 2, pp. 284-291. https://doi.org/10.1101/gr.2850605
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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.

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