Simultaneous genotyping, gene-expression measurement, and detection of allele-specific expression with oligonucleotide arrays.
Ronald J, Akey JM, Whittle J, Smith EN, Yvert G, Kruglyak L.
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
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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PMID: 15687292 [PubMed - indexed for MEDLINE]PMCID: PMC546530