Dk. Griffin et al., CHROMOSOME-SPECIFIC COMPARATIVE GENOME HYBRIDIZATION FOR DETERMINING THE ORIGIN OF INTRACHROMOSOMAL DUPLICATIONS, Journal of Medical Genetics, 35(1), 1998, pp. 37-41
Chromosome specific comparative genome hybridisation (CGH) is a novel
approach for the detection of cytogenetic abnormalities. It combines f
low sorting of chromosomes, degenerate oligonucleotide primed (DOP)-PC
R and a modified comparative genome hybridisation (CGH) technique to d
efine the site and extent of intrachromosomal duplications. Chromosome
specific paint probes for aberrant chromosomes and their normal homol
ogues from four subjects with unbalanced duplications within chromosom
es 2p11-15, 3q25-26, 5q34-qter, and 12q23-24.2 were made. They were th
en cohybridised on normal metaphase spreads and the ratio of their rel
ative intensities of hybridisation analysed. The results were compared
to those of similar experiments where regular CGH was performed on th
e same four patients. We provide evidence that this method can detect
duplications and deficiencies which might be missed by conventional CG
H, as the ratio of hybridisation of abnormal/normal DNA is 2:1 rather
than 3:2. It is the method of choice where mosaicism is present or whe
re only one of several homologous chromosomes is duplicated. Furthermo
re, it suggests that DOP-PCR amplifies all or most of the euchromatic
regions of the genome equally.