A cytogeneticist's perspective on genomic microarrays

Abstract

The identification of cytogenetic imbalance is an important component of clinical genetics. About 1 in 154 newborns has a chromosome abnormality. Conventional cytogenetic analysis has enabled the identification of microscopic alterations of the chromosomes. The development of fluorescence in situ hybridization (FISH) and other molecular methodologies has made possible the identification of submicroscopic aberrations. An additional development was comparative genomic hybridization (CGH), a method that directly compares two genomes for DNA copy differences. As first developed, the substrate for CGH analysis is normal metaphase chromosomes. Recently, CGH has been applied to microarrays (array CGH) constructed from large insert clones to identify chromosome imbalance. Array CGH has many advantages over conventional cytogenetic and molecular cytogenetic techniques. Array CGH can be comprehensive (genome-wide), high resolution, amenable to automation, rapid, and sensitive. We anticipate that array CGH will be employed in the clinical cytogenetics laboratory in the near future and will lead to the identification of the chromosomal basis of new syndromes and existing genetic conditions.