Array-comparative genomic hybridization
Array-comparative genomic hybridization (also CMA, Chromosomal microarray analysis, microarray-based comparative genomic hybridization, array CGH, a-CGH, aCGH, or virtual karyotype) is a technique to detect genomic copy number variations at a higher resolution level than chromosome-based comparative genomic hybridization (CGH).[1]
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[edit] Process
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.
[edit] Efficiency
Using this method, copy number changes at a level of 5–10 kilobases of DNA sequences can be detected [2] . Today 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
- duplications
in disease conditions such as cancer and birth defects due to chromosome aberrations.
[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 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.
[edit] First baby born from the procedure
In September 2009, it was reported that the first baby born after screening with this procedure using polar body biopsy analysis, was Oliver, who was born in the UK to a 41-year-old woman. Of eight eggs that had been tested from the woman, only two were found to be chromosomally normal, and one of those two was used to make the embryo that became Oliver. Prior to Oliver's birth, his mother had undergone 13 failed attempts at in vitro fertilization.[4] The procedure was overseen by CARE Fertility.
[edit] See also
[edit] References
- ^ 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. "BAC-based PCR fragment microarray: high-resolution detection of chromosomal deletion and duplication breakpoints". Human Mutation. http://www.ncbi.nlm.nih.gov/pubmed/15832308.
- ^ Urban, A.E., Korbel, J.O., Selzer, R., Richmond, T., Hacker, A., Popescu,G.V., Cubells, J.F., Green, R., Emanuel, B.S., Gerstein, M.B. (2006). "High-resolution mapping of DNA copy alterations in human chromosome 22 using high-density tiling oligonucleotide arrays". Proc. Natl. Acad. Sci. 103: 4534–39.
- ^ First baby born from new egg-screening technique, Breitbart, September 2, 2009
[edit] External links
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