Paediatrics: Chromosome tests

Chromosome tests

Karyotype analysis

A standard chromosome analysis involves a G-banded karyotype viewed by a cytogeneticist using a light microscope. Using this approach, the maxi-mum resolution is 75–10Mb. One of the major advantages of a chromo-some analysis is that it is a genomic survey, i.e. it looks in outline at the whole genome. The normal male karyotype is 46, XY. The normal female karyotype is 46, XX.

Fluorescence in situ hybridization (FISH)

Targeted studies are possible at higher resolution using specific FISH probes. Using FISH, it is possible to see the submicroscopic deletions re-sponsible for Williams syndrome (7q) and Angelman syndrome (15q), but only if the clinician specifically requests this.

Molecular kayotyping using microarrays

Microarray analysis is an ever improving technology which enables much higher resolution DNA analysis than is possible with light microscopy. It has recently started to be used in clinical practice and has been especially valuable to clinical geneticists in identifying patients with chromosomal ab-normalities previously not diagnosable by standard techniques. However, it is a specialist tool and is not routinely in use in paediatric settings. There are two main types of array:

Targeted arrays

These analyse selected regions of the genome, e.g. known syndromes and sub-telomeric regions.

Genome-wide arrays

These give genome-wide coverage at varying degrees of resolution ranging from 1Mb to 100kb, i.e. 10–100 times greater resolution than conventional light microscopy. It is important to appreciate that at high levels of reso-lution there is considerable normal variation in the human genome. Copy number variation is routinely identified both in pathological states and as normal family variants. Differentiating between the pathological and non-pathological variation is not within the compass of the non-specialist.