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Chromosome analysis: from karyotyping to microarray analysis

Although the introduction of molecular genetics and use of microarray technology in routine practice has largely replaced conventional karyotyping, there remains a place for the latter in 21st-century cytogenetics.

The analysis of the human genome has largely been undertaken in a research environment, but recent developments in technology and associated workflow have allowed diagnostic laboratories to interrogate DNA at significantly improved levels of resolution. Principally, whole genome-based analysis of copy number changes using microarrays has led to this method replacing conventional karyotyping as a routine diagnostic workhorse. The resolution offered by microarrays is an improvement of at least an order of magnitude compared to karyotyping, but it comes at a cost in terms of the time spent in data interpretation. However, the die has been cast and cytogeneticists are now required to be familiar with the tools used by molecular geneticists and bioinformaticists.

A brief perspective

Conventional cytogenetics has been based on the premise of phenotype first. In other words, the clinician identifies the suspected genetic abnormality and the laboratory will either confirm or refute the suspicion. Down’s syndrome is the classical example of this premise. John Langdon Down collected information on individuals displaying the characteristic 'Mongoloid' features with intellectual deficiency. It was not until the advent of conventional cytogenetics in which chromosomes could be analysed microscopically that Le Jeune et al. defined the genotype as having an additional chromosome 21 (trisomy 21).

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