title: Evaluation of the efficacy of constitutional array-based comparative genomic hybridization in the diagnosis of aneuploidy using genomic and amplified DNA.
abstract: OBJECTIVE
  Array-based comparative genomic hybridization (array CGH) is a new molecular technique that has the potential to revolutionize cytogenetics. However, use of high resolution array CGH in the clinical setting is plagued by the problem of widespread copy number variations (CNV) in the human genome. Constitutional microarray, containing only clones that interrogate regions of known constitutional syndromes, may circumvent the dilemma of detecting CNV of unknown clinical significance.
  
  
  METHODS
  The present study investigated the efficacy of constitutional microarray in the diagnosis of trisomy. Test samples included genomic DNA from trisomic cell lines, amplification products of 50 ng of genomic DNA and whole genome amplification products of single cells. DNA amplification was achieved by means of multiple displacement amplification (MDA) over 16 h.
  
  
  RESULTS
  The trisomic and sex chromosomes copy number imbalances in the genomic DNA were correctly identified by the constitutional microarrays. However, there was a failure to detect the trisomy in the amplification products of 50 ng of genomic DNA and whole genome amplification products of single cells.
  
  
  CONCLUSIONS
  Using carefully selected clones, Spectral Genomics constitutional microarray was able to detect the chromosomal copy number imbalances in genomic DNA without the confounding effects of CNV. The diagnostic failure in amplified DNA samples could be attributed to the amplification process. The MDA duration of 16 h generated excessive amount of biases and shortening the duration might minimize the problem.
authors.affiliation: Prince Court Medical Centre, Women and Children, Kuala Lumpur, Malaysia. niaphong@hotmail.com
authors.forename: Niap H
authors.initials: NH
authors.lastname: Tan
authors.forename: Rodger
authors.initials: R
authors.lastname: Palmer
authors.forename: Rubin
authors.initials: R
authors.lastname: Wang
mesh_terms: D000782:Aneuploidy; D002460:Cell Line; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D018076:DNA, Complementary; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D014314:Trisomy / Q000175:diagnosis*
chemical_list: D018076:DNA, Complementary