Widespread aneuploidy revealed by DNA microarray expression profiling

Expression profiling using DNA microarrays holds great promise for a variet y of research applications, including the systematic characterization of ge nes discovered by sequencing projects(1,2) To demonstrate the general usefu lness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants(3). Approximately 8% of the mutants profiled exhibited chromosome-wide expression biases, leading to sp urious correlations among profiles. Competitive hybridization of genomic DN A from the mutant strains and their isogenic parental wild-type strains sho wed they were aneuploid for whole chromosomes or chromosomal segments. Expr ession profile data published by several other laboratories also suggest th e use of aneuploid strains. In five separate cases. the extra chromosome ha rboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our r esults have implications for interpreting whole-genome expression data, par ticularly from cells known to suffer genomic instability, such as malignant or immortalized cells.