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Widespread aneuploidy revealed by DNA microarray expression profiling.
T R Hughes1, C J Roberts, H Dai
1Rosetta Inpharmatics, Inc., Kirkland, Washington, USA.
Nature Genetics
|July 11, 2000
Summary
DNA microarrays reveal that many yeast deletion mutants are aneuploid, causing inaccurate gene expression profiles. This highlights the need to validate genomic stability when analyzing expression data.
Area of Science:
- Genomics
- Molecular Biology
- Yeast Genetics
Background:
- DNA microarrays are valuable for gene expression profiling and characterizing novel genes.
- Systematic analysis of gene deletion mutants is crucial for understanding gene function.
Purpose of the Study:
- To assess the utility of DNA microarrays for expression profiling in Saccharomyces cerevisiae deletion mutants.
- To identify potential issues affecting the accuracy of expression data in mutant strains.
Main Methods:
- Expression profiling of nearly 300 Saccharomyces cerevisiae deletion mutants using DNA microarrays.
- Competitive hybridization of genomic DNA from mutant and wild-type strains to detect aneuploidy.
- Analysis of published expression data for evidence of aneuploid strains.
Main Results:
- Approximately 8% of profiled mutants showed chromosome-wide expression biases, indicative of aneuploidy.
- Aneuploidy was confirmed through genomic DNA hybridization, involving whole chromosomes or segments.
- Analysis of other studies revealed similar instances of aneuploid strains in expression profiling experiments.
- In some cases, extra chromosomes contained homologous genes to the deleted ones, conferring a growth advantage.
Conclusions:
- Aneuploidy is a significant factor that can lead to spurious correlations in gene expression profiles.
- Genomic instability, such as aneuploidy, must be considered when interpreting whole-genome expression data, especially in malignant or immortalized cells.
- The findings emphasize the importance of quality control for genomic stability in gene expression studies.