Abstract
Gene copy-number abnormalities (CNAs) are characteristic of solid tumors and are found in association with developmental abnormalities and/or mental retardation. The ultimate impact of CNAs is exerted by the altered expression of encoded genes. We have utilized high-density oligonucleotide arrays from Affymetrix to identify DNA CNAs via their impact on mRNA expression levels. In these studies, we have used three different trisomic cell lines (trisomy 9, trisomy 18, trisomy 21) as models of CNAs and have compared mRNA expression in those trisomic cells with that observed in diploid cell lines of matched tissue origin. Our data clearly show that genes from CNA chromosome regions are substantially over-represented (P<0.000001 by chi-square analysis) in the differentially expressed subset from comparisons of all three trisomic cell lines with normal matching cells. In addition, we have been able to detect the origin of the duplication by a statistical scan for over-expressed genes. These data show that microarray detection of differential mRNA expression can be used to identify significant DNA CNAs.
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Acknowledgments
This work was supported in part by NIH PHS grants R21 CA94216 (to D. Wong), R21 AI49135, and R01 AI52737 (to S. Cole), and NIH training grant DE07296-07 and a CRFA fellowship (to X. Zhou). The Affymetrix U133A array hybridization and scanning were performed in the UCLA DNA microarray facility.
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Zhou, X., Cole, S.W., Hu, S. et al. Detection of DNA copy number abnormality by microarray expression analysis. Hum Genet 114, 464–467 (2004). https://doi.org/10.1007/s00439-004-1087-9
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DOI: https://doi.org/10.1007/s00439-004-1087-9