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The achievements by Patrick O. Brown and Stephen P.A. Fodor provide methods that enable the simultaneous analysis of sequences and functions of large numbers of genes. Life processes are controlled with expression and suppression of genes in interacted fashions and without DNA microarrays it was almost impossible to analyze dynamic expression and interactions of genes due to changes in environment surrounding cells. DNA microarrays enable researchers to follow time courses of expression of multiple genes under different conditions in quantitative and simultaneous fashions. Their methods represent a significant technical jump from previous technologies. The main application fields of DNA microarrays are gene expression analysis and genetic analysis. In gene expression analysis, the gene expression "scripts" that specify the distinctive properties and behavior of each different cell in our bodies, and the changes in gene expression during development, in physiological responses, and in disease, can be followed with DNA microarrays by monitoring the messenger RNAs that specify which proteins are made in each cell, and in what amounts. Changes in gene expression due to pathological processes such as cancer and viral diseases, and due to cellular responses to medication, can be visualized by DNA microarrays as changes in the fluorescent pattern. The application of DNA microarrays to drug discovery, diagnosis and therapy has already begun.
DNA microarrays are also used to detect small differences in genes (single nucleotide polymorphism, SNP) between individuals, which exist in one to hundreds or thousands in genes and correspond to expression differences in individuals. SNP research is very important, because it can lead to tailor-made medications, in which an individual can be diagnosed and treated according to his or her own genetic information.
DNA microarrays are very small glass or silicon supports with hundreds of thousands of different oligonucletides or cDNAs on their surface. Target DNA or RNA from a sample mixture binds to certain oligonucleotides or cDNAs on the surface, and these are identified by detecting emission from a fluorophore attached to the target. The methods utilize hybridization, base pair formation in which complementary strands of DNA bind together. Target DNAs or RNAs are identified by their positions on the surface, and the quantity of each target is measured by the strength of its emission.
In 1991, Stephen P. A. Fodor reported the fabrication of DNA microarrays by combining the photolithographic method, used in semiconductor fabrication, and combinatorial synthesis of oligonucleotides on the surface of glass chips, while working for Affymax, an early combinatorial chemistry venture. In 1993, he co-founded Affymetrix, a spin-off of Affymax, in order to develop oligonucleotide arrays with hundreds of thousands of oligonucleotides on the surface of the supports. In 1994, Affymetrix commenced manufacturing and selling the first DNA microarray, GeneChip®, thus realizing the DNA microarray market.
Patrick O. Brown developed an idea for mechanically arraying cDNA on the surface of a glass support so that researchers could prepare DNA microarrays mounting their choice of array content. He led his research group to develop a method for fabricating DNA microarrays utilizing a robot to spot numerous cDNAs on the surface of easily available slide glass. In 1996, he disclosed the know-how, tools, and designs for the fabrication of DNA microarrays on the Internet so that scientists could make their own DNA microarrays in their own laboratories. This disclosure of information for the self-fabrication of DNA microarrays has prompted the wide-spread use of DNA microarrays with pre-synthesized probes.
The uses of DNA microarrays developed by Brown and Fodor have different features and complement each other. Commercialization of the GeneChip® array and promotion of self-made DNA microarrays by disclosing information on the Internet have synergistically prompted the wide-spread use of DNA microarrays. DNA microarrays have been used not only in the field of medicine, but also in the field of agriculture for the purposes of effective breeding and increasing tolerance to the environment. Their achievements deserve the Takeda Award. |
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