Array comparative genomic hybridization

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Array comparative genomic hybridization
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Array comparative genomic hybridization (also CMA, Chromosomal
Microarray Analyisis, Microarray-based comparative genomic
hybridization, array CGH, a-CGH, or aCGH) detects genomic copy number
variations at a higher resolution level than chromosome-based
comparative genomic hybridization (CGH).[1]

Contents [hide]
1 Process
2 Efficiency
3 Technical considerations
4 See also
5 References
6 External links



[edit] Process
DNA from a tumor sample and normal reference sample are labelled
differentially, using different fluorophores, and hybridized to
several thousand probes. The probes are derived from most of the known
genes and non-coding regions of the genome, printed on a glass slide.

The ratio of the fluorescence intensity of the tumor to that of the
reference DNA is then calculated, to measure the copy number changes
for a particular location in the genome.


[edit] Efficiency
Using this method, copy number changes at a level of 5-10 kilobases of
DNA sequences can be detected. This method allows one to identify new
recurrent chromosome changes such as

microdeletions
amplifications
in disease conditions such as cancer and birth defects due to
chromosome microdeletions.


[edit] Technical considerations
There are several requirements that are dependent on the application
of aCGH:

Complexity. Measurement becomes difficult in larger organisms because
of decreasing partial concentrations of each portion of the sequence
that is involved in the hybridization to the array element as the size
of the genomes increase. This issue may be addressed by increasing the
threshold in which one detects only larger increases in copy number of
DNA extracted from cells, but this comes at the cost of increasing
failure to detect low level gains and losses.
Samples. Tissue specimens may contain heterogeneous cell populations,
which may further decrease the ability to detect copy number change in
genes in the aberrant tumor cells because the population may contain
normal cells. Furthermore, the use of tissue from clinical specimens
severely limit the amount of DNA available for analysis.
Error tolerance. If the investigator is set to obtain a generalized
description of aberrations that may occur in a set of samples, then
errors in the detection may not be critical. However, the margin for
error is drastically narrowed in a clinical setting, where an
individual specimen is used to obtain specific information.

[edit] See also
Comparative genomic hybridization
DNA
Genome

[edit] References
^ Shinawi M, Cheung SW (2008). "The array CGH and its clinical
applications". Drug Discov Today. doi:10.1016/j.drudis.2008.06.007.
PMID 18617013.

[edit] External links
A bibliography on copy number variation
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