A comparison of different metaphase CGH methods for the detection of cryptic chromosome aberrations of defined size

Eur J Hum Genet. 2004 Jun;12(6):447-54. doi: 10.1038/sj.ejhg.5201175.


An increasing body of evidence indicates that submicroscopic gene dose alterations may cause mental impairment and malformations. During the last decade, comparative genomic hybridization (CGH) has become a useful tool in the detection and mapping of chromosome aberrations. Modifications of CGH with increased resolution down to 3-5 Mb have been reported and CGH is now offered as a diagnostic procedure in the evaluation of patients with idiopathic mental retardation (MR). In order to increase the resolution, we modified the CGH protocol using freshly prepared high-quality metaphase slides and chemical labeling, and tested the method on a set of patients with well-defined submicroscopic chromosome abnormalities with confirmed size 1.3-20.5 Mb. Subsequently, a completely blinded test was performed to compare the performance of the chemical labeling CGH to the commercially available HR-CGH. Using the two different CGH methods, we were able to detect chromosome imbalances down to 2-3 Mb approximately. The HR-CGH method detected all aberrations >6 Mb and a few smaller, while the modified CGH method was able to detect all but three aberrations >1.8 Mb. The modified CGH method was superior in the detection of terminal imbalances, while the HR-CGH software was more successful in the detection of imbalances located very close to the centromeric regions. In conclusion, the resolution of metaphase CGH may be as high as 2-3 Mb but is most likely depending on the chromosomal region involved, a clear limitation when used as a screening method for chromosome aberrations in patients with idiopathic MR.

Publication types

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

MeSH terms

  • Chromosome Aberrations*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • Chromosome Mapping
  • Genetic Markers
  • Humans
  • In Situ Hybridization, Fluorescence
  • Metaphase
  • Nucleic Acid Hybridization / methods*
  • Syndrome


  • Genetic Markers