Array-comparative genomic hybridization
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It has been suggested that this article be merged into Comparative genomic hybridization. (Discuss) Proposed since July 2012. |
For a more comprehensive overview of Array CGH techniques and applications refer to Comparative genomic hybridization#Array Comparative Genomic Hybridization.
Array-comparative genomic hybridization (also CMA, Chromosomal microarray analysis, microarray-based comparative genomic hybridization, array CGH, a-CGH, aCGH) is a technique to detect genomic copy number variations at a higher resolution level than chromosome-based comparative genomic hybridization (CGH).[1] It can be used to create a virtual karyotype.
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Process [edit]
DNA from a test 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 fluorescence intensity of the test and of the reference DNA is then measured, to calculate the ratio between them and subsequently the copy number changes for a particular location in the genome.
Efficiency [edit]
Using this method, copy number changes at a level of 5–10 kilobases of DNA sequences can be detected.[2] As of 2006[update], even high-resolution CGH (HR-CGH) arrays are accurate to detect structural variations (SV) at resolution of 200 bp.[3] This method allows one to identify new recurrent chromosome changes such as microdeletions and duplications in human conditions such as cancer and birth defects due to chromosome aberrations.
Technical considerations [edit]
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 limits 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.
See also [edit]
References [edit]
- ^ Shinawi M, Cheung SW (2008). "The array CGH and its clinical applications". Drug Discov Today 13 (17–18): 760–70. doi:10.1016/j.drudis.2008.06.007. PMID 18617013.
- ^ Ren H, Francis W, Boys A, Chueh AC, Wong N, La P, Wong LH, Ryan J, Slater HR, Choo KH (May 2005). "BAC-based PCR fragment microarray: high-resolution detection of chromosomal deletion and duplication breakpoints". Human Mutation 25 (5): 476–82. doi:10.1002/humu.20164. PMID 15832308.
- ^ Urban AE, Korbel JO, Selzer R, Richmond T, Hacker A, Popescu GV, Cubells JF, Green R, Emanuel BS, Gerstein MB, Weissman SM, Snyder M (21 March 2006). "High-resolution mapping of DNA copy alterations in human chromosome 22 using high-density tiling oligonucleotide arrays". Proc Natl Acad Sci U S A 103 (12): 4534–4539. doi:10.1073/pnas.0511340103. PMC 1450206. PMID 16537408.
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