Applications of comparative genomic hybridisation in constitutional chromosome studies

G band cytogenetic analysis often leads to the discovery of unbalanced kary otypes that require further characterisation by molecular cytogenetic studi es. In particular, G band analysis usually does not show the chromosomal or igin of small marker chromosomes or of a small amount of extra material det ected on otherwise normal chromosomes. Comparative genomic hybridisation (C GH) is one of several molecular approaches that can be applied to ascertain the origin of extra chromosomal material. CGH is also capable of detecting loss of material and thus is also applicable to confirming or further char acterising subtle deletions. We have used comparative genomic hybridisation to analyse 19 constitutional chromosome abnormalities detected by G band a nalysis, including seven deletions, five supernumerary marker chromosomes, two interstitial duplications, and five chromosomes presenting with abnorma l terminal banding patterns. CGH was successful in elucidating the origin o f extra chromosomal material in 10 out of 11 non-mosaic cases, and permitte d further characterisation of all of the deletions that could be detected b y GTG banding. CGH appears to be a useful adjunct tool for either confirmin g deletions or defining their breakpoints and for determining the origin of extra chromosomal material, even in cases where abnormalities are judged t o be subtle. We discuss internal quality control measures, such as the mism atching of test and reference DNA in order to assess the quality of the com petitive hybridisation effect on the X chromosome.