Expression profiling using DNA microarrays holds great promise
for various research applications, including the systematic
characterization of genes discovered by sequencing projects. To
demonstrate the general utility of this approach, we recently obtained
expression profiles for nearly 300 S. cerevisiae deletion
mutants, most of which were obtained through the Saccharomyces
Genome Deletion Consortium (Hughes et al., in press). To our
surprise, ~8% of the mutants profiled exhibited chromosome-wide
expression biases, leading to spurious correlations among
profiles. Competitive hybridization of genomic DNA from the mutant
strains and their isogenic parental wild-type strains showed they were
aneuploid for one or more chromosomes. Expression profile data
published by at least four other laboratories also contained
chromosome-wide expression biases consistent with aneuploidy. In five
distinct cases of aneuploid mutants, the extra chromosome harbored a
close homolog of the deleted gene; in two of these, a clear growth
advantage for cells harboring the extra chromosome was
demonstrated. Expression biases within chromosomes (i.e., segmental
aneuploidy) were also observed, including one mutant that contained a
small duplication most likely a result of selection for a homologous
recombination event. These results have implications for interpreting
whole-genome expression data, particularly from cells known to suffer
genomic instability, such as malignant or immortalized cells.
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