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