Array CGH for Dummies

Array-CGH (Comparative Genomic Hybridasation) is becoming a common method used for analysis of patients’ genomes. Array-CGH works by taking a reference genome covering the whole human genome sequence, cutting it into thousands of pieces and orderly attach them to a chip. These pieces are called probes and are usually on the range of 500-2000 DNA bases long. A saliva or blood sample is then taken from the patient and its DNA is also chopped into thousands of pieces in suspension with a solvent. The array is then washed with the suspension containing the patient’s DNA.

DNA is a double chain of nucleotide bases where one chain complements the other. Knowing one chain of the DNA, it is possible to know the other chain. In its natural state, a single DNA chain will tend to bind to its complementary chain. Thus, by washing the patient’s suspension with the array probes will make the patient’s DNA pieces bind to its complementary DNA in the array.

Picture 4Array-CGH can be used to detect whether a patient has a region of the genome missing or duplicated. Probes attached to the chip emit a different color depending on their state of binding. Once the array is washed, most of probe spots will appear yellow, that is, all different probes of the reference genome are bound to the patient’s DNA. If a DNA region is missing in the patient, the complementary spots in the array appear in red. These changes appear in sequential order mapping to the reference genome missing in the patient. Depending on the genes that overlap to the deletion, different symptoms may appear in the patient.

The same happens if the array shows a series of green spots, indicating that a duplicated region of the genome has been found in the DNA of the patient. Because the gene content will be altered in the duplicated region, this may cause disease as a consequence of the over-expression of genes included in the duplicated regions.

Thus, using array techniques, we are now able to find deletions or duplications in the genome of a patient beyond the microscopic level, i.e. changes not directly observable. We are all familiar with the features of a patient with Down’s Syndrome. This syndrome is caused because there is an extra copy of chromosome 21 in the affected patient, due to a duplication of one of the two usual copies (Trisomy 21).

Most of the chromosomal deletions and duplications occur at the molecular level [1], not identifiable with microscopic techniques, as in the case of Down’s Syndrome. Up until recently most of the patients suspected of suffering from genomic diseases, i.e. diseases caused by pathogenic deletions or duplications, went undiagnosed because techniques did not allow detection beyond big chromosomal changes (like whole chromosomes). Techniques such as array-CGH now allow detection of chromosomal changes a thousand times smaller in length.

For a price of about £100 per array one can have one’s genome screened for chromosomal changes. In fact, it seems that most of the genetic changes between any two people (in terms of number of DNA bases) is dependent on the level of micro- deletions and duplications (called Copy Number Variations) [2], just the level we are now starting to handle with current analysis techniques. Next generation sequencing technologies are fast arriving that will allow the base-by-base complete sequencing of the DNA of people at price of $1000 in a short period of time [3].

[1] H.V. Firth, S.M. Richards, A.P. Bevan, S. Clayton, M. Corpas, D. Rajan, S. Van Vooren, Y. Moreau, R.M. Pettett, N.P. Carter (2009). DECIPHER: DatabasE of Chromosomal Imbalance and Phenotype using Ensembl Resources. The American Journal of Human Genetics.

[2] J. R. Lupski (2009). Genomic disorders ten years on.  Genome Medicine

[3] Mardis E.R. (2006). Anticipating the 1,000 dollar genome. Genome Biology

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