What are DNA Microarrays? The Science - How do DNA Microarrays Work? What is Gene Expression and How is it Used? Biotechnology and DNA Microarrays Uses of DNA Microarrays Bibliography

In the past, scientists have only been able to conduct genetic analyses on a few genes at once. The development of DNA microarray technology allows scientists to examine thousands of genes at the same time, an advance that will help them determine the complex relationships between individual genes.

One of the most important benefits of DNA microarrays lies in their ability to measure the expression of a large number of genes with great efficiency. Microarrays permit scientists to assess the relative expression levels of hundreds, even thousands, of genes in a single experiment.

DNA microarrays are also called DNA chips, gene chips, and bio chips.

 

What are DNA Microarrays?

DNA microarrays are stamp-sized glass or silicon microchips that are imbedded with thousands of single-stranded DNA, each placed at a specific location on the chip in grid formation. The identities and locations of the single-stranded DNAs are known. The chip is immersed in a solution prepared from a patient's sample (usually blood), and if a particular DNA strand from the solution is complementary to the ones on the chip, a bond will occur on that specific spot. Since scientists know that each grid represents a certain DNA, a bond indicates that that particular sequence of DNA is present in the sample given by the patient.

The Science - How do DNA Microarrays Work?

DNA microarray technology is possible because scientists have found a way to use the natural characteristics of DNAs to bond in a complementary fashion. DNA is made of smaller parts called nucleotides which are strung together into a strand. A fully functioning DNA has two of these strands that are attached to each other at every nucleotide point. There are four different types of nucleotides: adenine, guanine, cytosine, and thymine, commonly known as A, G, C, and T. These nucleotides can only bond from one strand to the other in one way: A always bonds with T, and C always bonds with G. It is this complementarity that makes them useful in diagnostics, like the DNA microarray.

Learn more about the Binding Characteristics of DNA and Proteins

DNA microarrays are used extensively to measure the expression level of a particular gene or genes.

What is Gene Expression and How is it Used?

Gene Expression

Expressed genes are those that have been turned into proteins, which are the functional products of genes. A gene may code for something to happen, but in order for that something to happen, a protein must be produced to do the work.

Every single cell in the body has the same set of genes. However, different genes are active (and therefore "expressed") in different kinds of cells and tissues. In the process of having certain genes expressed, the cell uses several proteins. One of these is called a messenger RNA (mRNA for short) and it is only produced when a gene is being turned into a protein. This is how a DNA microarray can detect the level of expression of a certain gene - by testing for the presence and level of mRNAs associated with that particular gene.

Changes in a cell's environment can trigger the production of a protein. Once the cell is ready to make a certain protein, a segment of the double-stranded DNA, which is responsible for that code, unravels so that it temporarily becomes two single strands. Then, mRNAs make a complementary copy of one single strand of DNA, nucleotide by nucleotide. The mRNA, which is then an exact complementary version of the DNA strand, travels to another part of the cell where its genetic information is used to construct a particular protein.

The more a gene is translated into protein, the more copies of mRNA are present inside the cell. This level of mRNA can be measured by microarrays which are imbedded with a known set of DNA.

Where the Chip Comes In

A specific tissue sample is taken from the patient. The mRNA from the tissue is changed into complementary DNA (cDNA), which is easier to work with. At this point, the mRNA and cDNA represent the same information from the patient, just in a different form. This cDNA is then tagged with radioactive molecules so that they can be detected later. This is called labelling.

When the DNA microarray is dipped into the solution of cDNA made from the patient's sample, the cDNAs that are complementary to the DNA on the chip will bond. Because scientists know which DNAs are imbedded on the chip, a bond with a certain DNA indicates the expression of a particular DNA sequence in the patient's cell or tissue. Finally, the microarray is inserted into an instrument that can read the presence and location of the radioactive molecules.

Biotechnology and DNA Microarrays

Two key biotechnology advances stand out in the making of DNA microarrays:

• Genomics -- This is the study of the whole set of human genes. Although DNA microarrays have benefited from gene discoveries through projects such as the Human Genome Project, genomics may also help in the discovery of the function of those genes.
  
  What is Genomics?
  
  
• Immobilization Technology -- This technology refers to the binding of cells and other biological molecules, such as DNA strands, to a solid matrix, such as glass. Immobilization techniques must preserve the biological activity of the molecules to be useful. In making DNA microarrays, one such technique is used more often than others. It is called photolithography and it was developed by Affymetrix Inc.

Uses of DNA Microarrays

DNA microarrays have many uses. If scientists know that an overexpression of a certain gene is the cause of a disease, they can test a tissue sample to see if this is the case. As well, they can compare the DNA microarray results of two samples, such as one from a normal tissue, and another from a diseased tissue and see which genes are expressed, overexpressed or underexpressed. It is an effective way to find out which genes are involved in certain diseases.

Here are examples of its uses:

Use: Identification of tissue-specific genes

Explanation: Different cells and tissues express different genes. Therefore, the gene expression of different tissues and cells can be compared.

Use: Analysing gene regulation in cancer

Explanation: Genetic diseases can be the result of too much or too little expression of a certain gene. In cancer, diseased cells may be studied for expression levels of certain cancer-related genes.

Use: Pharmaceutical analysis

Explanation: Used to study the relationship between a person's response to specific drugs and the genetic make-up of that person. As well, more effective drug targets can be studied by analysing the gene expression after toxin or drug exposure.

Bibliography

How do DNA chips work? University of Waterloo 19 June 2001 sciborg.uwaterloo.ca/~bpbobech/mech.html

Kaur, Baldish. "DNA Microarray Technology". University of Leeds 19 June 2001 www.fbsmres.leeds.ac.uk/users/bmbbk/baldish/dnamicroarrays.html NHGRI Fact Sheet.

Biochips. Advanced Array Technology 21 June 2001 in www.aat-array.com/biochips%20for%20beginners.htm

Cummings, Craig A. and David A. Relman. "Using DNA Microarrays to Study Host-Microbe Interactions." Emerging Infectious

Diseases, Center for Disease Control www.cdc.gov/ncidod/eid/vol6no5/cummings.htm

DNA Microarrays - Introduction. Trueforce 19 June 2001 trueforce.com/lab_automation/dna_microarrays.htm

Changing Conditions and Industry Response. The Biotechnology Gateway, Industry Canada 12 June 2001 strategis.ic.gc.ca/ssg/bo01291e.html

Debouck, Christine and Peter N. Goodfellow. "DNA microarrays in drug discovery and development" Nature Genetics 12 June 2001 www.nature.com/cgi-taf/dynapage.taf?file=/ng/journal/v21/n1s/full/ng0199supp_48. html

Gluing Cells to Biochips can make diagnostic devices. Daily University Science News 12 June 2001 unisci.com/stories/20003/0925002.htm

Anatomy of a Comparative Gene Expression Study. Department of Computer Science and Engineering, University of Washington 14 June 2001 www.cs.washington.edu/homes/jbuhler/research/array

Cross-Cutting Science: Paving the Way to Discovery. National Institute of Diabetes & Digestive & Kidney Diseases 12 July 2001 www.niddk.nih.gov/federal/advances/cross.pdf

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Steinberg, Douglas. "DNA Chips Enlist in War on Cancer." The Scientist February 21,2000. 12 June 2001 www.the-scientist.com/yr2000/feb/steinberg_p1_000221.html

Lander, Eric S. "Array of Hope." Nature Genetics Volume 21. 12 June 2001 www.nature.com/cgi-taf/dynapage.taf?file=/ng/journal/v21/n1s/full/ng0199supp_3.html