Detection of DNA copy number abnormality by microarray expression analysis

Hum Genet. 2004 Apr;114(5):464-7. doi: 10.1007/s00439-004-1087-9. Epub 2004 Feb 11.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18 / genetics*
  • Chromosomes, Human, Pair 21 / genetics*
  • Chromosomes, Human, Pair 9 / genetics*
  • Gene Dosage*
  • Humans
  • Oligonucleotide Array Sequence Analysis / methods*
  • Trisomy / genetics*