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DNA Microarrays, an Introduction :
Introduction to Microarrays
Availability of whole genomic sequences from many organisms (such as the human genome project) have created the need for high throughput analysis of gene expression patterns.
DNA microarrays have revolutionized functional and genomic analysis.
The Evolution of the DNA Microarray:
In the 1980's, bacterial colonies were spotted on nylon membranes with different genomic inserts or cDNAs
The 1990's resulted in the emergence of ink-jet spotting methods which allowed the in situ synthesis of 60-mer oligo spots on glass slides.
Affymetrix further developed DNA microarrays which were based on high-density 25-mer oligos from human cDNA sequences.
Background on DNA Microarrays
The basic premise of the DNA microarray is that RNA samples or targets are hybridized to known cDNAs/oligo probes on the arrays.
Microarrays were originally designed to measure gene expression levels of a few genes. Recently, high density microarrays have been developed which have allowed the global analysis of gene expression or the transcriptome. This global analysis allows one to determine the cellular function of genes, the nature and regulation of biochemical pathways, and the regulatory mechanisms at play during certain signalling conditions or diseases.
Regulation of Transcription and DNA Microarrays
The Human Genome Project has allowed a vast wealth of information to come into our hands. However, a huge problem is analyzing the new genes and putative regulatory functions of these genes. DNA microarray analysis has allowed these newly annotated genes and novel genes to be examined. New regulatory pathways can be examined using DNA microarrays. For example, the new gene may be a transcriptional factor. Microarrays can examine the effect that gene has on thousands of genes at a time, under many conditions in a simple and fast manner.
Applications of DNA Microarrays
DNA microarrays have been used to examine the gene expression changes under diseases such as cancer. Tumour profiling using DNA microarrays allows the analysis of the development and the progression of such complex diseases.
Using DNA microarrays, one can examine targets for drug discovery and potential diagnostic and prognostic biomarkers for many complex diseases.
DNA microarrays are used commonly to detect viruses and other pathogens from blood samples and thus can be used as a pathogen detection method.
DNA microarrays have been more recently used to identify inheritable markers, and therefore have been used as a genotyping tool.
SNP chips based on DNA microarray technology have allowed the high throughput profiling of single nucleotide polymorphisms using a chip or array approach. This has allowed polymorphisms to be more quickly assayed and also their relavence to disease to be easily determined.
Advantages of DNA Microarrays
DNA microarrays are better than other profiling methods (such as SAGE, SH, PCR methods) in that they are:
- easier to use
- are high-throughput (can analyze thousands of genes or markers at a time)
- generate large amounts of data in little time
- do not require large-scale sequencing
- allow the quantitation of thousands of genes from many samples