What is DNA chipping?
A DNA chip is a small solid support, usually a membrane or glass slide, on which sequences of DNA are fixed in an orderly arranged. DNA chipping analysis involves breaking open a cell, isolating its genetic contents, identifying all the genes that are turned on in that particular cell, and generating a list of those gene. With this method scientists can determine if there’s a mutation, like BRA1, is found in the genes. DNA chipping can also be used to determine which genes are turned off or turned on in cells and tissues. In this case, instead of isolating DNA from the samples, RNA is isolated and measured. When the cell or tissue contains mRNA the gene is turned off. Nowadays DNA chipping is also used in clinical diagnostics tests for some diseases. Sometimes they are also used to determine which drugs might be prescribed for someone, because the genes determine how our bodies handle the chemistry related to those drugs.
How does a DNA microarray work?
To determine whether an person has a mutation, a scientist first gets a sample of DNA from the patient's blood and a normal sample, which doesn’t contain a mutation.
The researcher then denatures the DNA in the samples. This is a process that separates the two complementary strands of DNA into single-stranded molecules. The next step is to cut the long strands of DNA into smaller parts and then to label each part by attaching a bright colour. The person’s DNA is labelled with red colour and the normal DNA is labelled with green colour. Both sets of labelled DNA are then inserted into the chip.
If the person doesn’t have a mutation for the gene, both the red and green samples will bind to the sequences on the chip. If the person does have a mutation, his or her DNA will not bind properly in the region where the mutation is located. The scientist can then examine this area more closely to prove that a mutation is present.
As you can see on the picture, a DNA microarray has a lot of spots in different colours on it. Those colours have a meaning:
‘ Green: the gene is only active in the normal sample.
‘ Red: the gene is only active in the diseased sample.
‘ Black: the gene isn’t active in either sample.
‘ Yellow: the gene is active in both samples.
History
The earliest form of the DNA microarray is the Southern blot, developed by Edward Southern in 1975. Southern blotting is a process where fragmented DNA is attached to a substrate and then probed with a DNA sequence.
In 1991, Stephen Fodor (see picture) showed that a diverse set of oligonucleotides (short DNA or RNA molecules used for genetic testing, research and forensics) could be chemically synthesized on a glass slide through photolithography. This is a process using exactly the right amount of light to move chemical reactions to specific spots. Now miniaturization was possible, because the density of spots was limited only by the diffraction of light.
Miniaturized microarrays were introduced in 1995. Patrick brown used a microarray of 45 complementary DNAs which they combined with fluorescently-labeled mRNA. The amount of fluorescence at a spot showed the amount of mRNA hybridized and that again showed the amount of mRNA in the initial sample.
In 1996, the first human gene expression microarray study was published and Affymetrix, an American company, released its first GeneChip microarray, for HIV. In 1997, Stanford researchers published the first whole-genome microarray study of yeast. In 1998, Brown’s lab developed cluster, a tool for microarray data analysis. By forming clusters you can discover groups in data. For the DNA microarray red and green spots separated the data in two groups.
Over the next years (1999-2003) the DNA microarray developed further. For example: DNA microarrays were now also used to classify cancers, to indentify the SARS virus can and it was now used in clinical practices. Since 2004 it is possible to have a whole human genome on one DNA chip.
Costs
DNA microarrays cost about $100 per sample for basic genomic studies, and up to $300 per sample for more complex studies. Microarrays can save money by targeting DNA instead of the entire genome. A targeted DNA microarray costs from $10 to $100 per sample, while a whole human genome is usually from $100 to $1000 per sample.
Affymetrix GeneChip
Affymetrix is an important manufacturer of DNA microarrays. The American company was founded by Stephen Fodor in 1992. A well-known and important invention of Affymetrix is the GeneChip microarray. The GeneChip is a DNA chip which assists researchers by (quickly) looking for the presence of particular genes in a sample. Within this area, Affymetrix focuses on oligonucleotide microarrays. These microarrays are used to determine which genes are present in a sample by indentifying pieces of mRNA. One chip can be used to analyze thousands of genes, but these chips can be used only once.
Disadvantages and advantages
DNA chipping is very difficult and to succeed in this, a close collaboration between surgeons, pathologists molecular biologists and bio-informaticists is required. To make sure that the outcome is accurate and reliable, it is essential that the experiments are organized and controlled often. This is also one of the reasons for DNA chipping being so expensive, which is for most people another con. Because DNA chipping is still such a difficult technology, the outcome might not always be accurate. It might take a long take to get an outcome, which is for some people another con. However, DNA chipping technologies are rapidly improving and the costs of DNA chipping continues to decrease.
What for some people might be a disadvantage, can be an advantage for other people. DNA chipping consists of only one undertaking. Instead of going through a whole trial, for examples MRI scans, DNA chipping only requires one. This makes DNA chipping also a lot faster, even though the outcome might take a while. Another advantage is that DNA chipping provides data for thousands of genes. This is very useful for a lot of scientists, because with the data that is provided by DNA chipping the scientists might eventually find a cure for diseases and cancer.
Own opinion
Rebekka
I think that DNA microarrays are a very good discovery, because it’s used for a lot of good things. You know if there’s a chance of you having cancer or that you already have it. If you know there’s a chance of you having cancer you can maybe prevent it by, for example, amputating your breasts (in the case of breast cancer). It has also helped researchers to developed new things which can, in the future, maybe also be used in clinical practices. DNA chipping is already faster than the old experiments, but I hope that they can develop it further so it will be even faster, it will be more accurate and it will be cheaper, so that the most people can afford it. I don’t think there’s anything bad about this DNA chipping.