Widespread aneuploidy revealed by DNA microarray expression profiling

Abstract

Expression profiling using DNA microarrays holds great promise for a variety of research applications, including the systematic characterization of genes discovered by sequencing projects. To demonstrate the general usefulness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants. Approximately 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 whole chromosomes or chromosomal segments. Expression profile data published by several other laboratories also suggest the use of aneuploid strains. In five separate cases, the extra chromosome harboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our results have implications for interpreting whole-genome expression data, particularly from cells known to suffer genomic instability, such as malignant or immortalized cells.

Promoter-dependent Roles for the Srb10 Cyclin-dependent Kinase and the Hda1 Deacetylase in Tup1-mediated Repression inSaccharomyces cerevisiae

“…The wild-type control strain used in that study was later shown to have a duplicated chromosome XIII, which resulted in all the genes on chromosome XIII seeming to be slightly down-regulated in a tup1⌬ strain (Hughes et al, 2000b). To correct for this strain abnormality and because microarray techniques and analysis have advanced since that first publication, we present a new set of expression microarray data for a tup1⌬ mutant.…”

The contribution of farm animals to human health

“…Meanwhile improvements of RNA isolation and unbiased amplification of tiny amounts of mRNA (picogram) enable researchers to analyse RNA from single embryos [90]. With the aid of this technology one can gain in-depth insight into the proper functioning of a transgenic organism and thereby ensure the absence of unwanted side effects [88,89]. This would also be required to maintain the highest possible levels of animal welfare in cases of genetic modification.…”

“…Furthermore, it should be kept in mind that the biomedical applications of farm animals will require strict standards of 'genetic security' and reliable and sensitive methods for the molecular characterization of the products. A major contribution towards the goal of well-defined products will come from array technology (cDNA, peptide or protein arrays), which establishes 'fingerprint' profiles at the transcriptional and/or protein level [88,89]. Meanwhile improvements of RNA isolation and unbiased amplification of tiny amounts of mRNA (picogram) enable researchers to analyse RNA from single embryos [90].…”

Global Transcription Analysis of Krebs Tricarboxylic Acid Cycle Mutants Reveals an Alternating Pattern of Gene Expression and Effects on Hypoxic and Oxidative Genes

“…The microarray datasets were investigated to test for chromosomal aneuploidy in the TCA cycle mutant strains (Hughes et al, 2000). Gene expression ratios from individual microarray experiments were sorted by chromosome, and the average expression for each chromosome was calculated to test for chromosome-wide expression bias indicative of chromosomal aneuploidy.…”