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A '''DNA microarray''' (also '''DNA chip''' or ''gene chip'' in common speech) is a piece of [[glass]] or [[plastic]] on which single-stranded pieces of [[DNA]] have been affixed in a microscopic [[array]].
MachinesScientist use such chips to screen a biological sample for the presence of many [[genetic sequence]]s at once. The affixed DNA segments are known as ''probes.'' HundredsThousands of identical probesprobe molecules are affixed at each point in the array to make the chips effective detectors.
Although the name "GeneChip" is a trademark of [[Affymetrix]], microarray users generally use this term, or simply "chip", to refer to any microarray, not just those sold from aby companyAffymetrix. While Affymetrix arrays areuse limitedshort tooligonucleotide featuring small oligonucleotidesprobes of less25 thanbases 25or basesless, many microarrays consist ofuse [[PCR]] products, genomic DNADNAs, [[Bacterial artificial chromosome|BACs]], [[plasmid]]s, or longlonger oligos (35 to 70 bases). Microarrays may be made by any number of technologies, including simple printing with fine-pointed pins onto glass slides, photolithography using pre-made masks, photolithography using dynamic micromirror devices, or ink-jet printers. MicroarraysThe use of microarrays for expression profiling was first published in 1995 (Science) and the first complete eukaryotic genome (Saccharomyces cerevisiae) on a microarray was published in 1997 (Science).
Typically arrays are used to detect the presence of [[mRNA]]s that may have been [[transcription|transcribed]] from different genes and which encode different proteins. The RNA is extracted from many cells, ofhopefully from a single cell type, then converted to cDNA andor cRNA. The copies may be "amplified" in [[concentration]] by [[RT-PCR|rtPCR]]. [[Fluorescent tag]]s are enzymatically incorporated into the newly synthesized strands or can be chemically attached to the new strands of DNA or RNA. A cDNA or cRNA [[molecule]] that contains a sequence complementary to one of the single-stranded probe sequences will hybridize, or stick, via ''base pairing'' (more at [[DNA]]) to the spot at which the complementary probes are affixed. The spot will then [[fluorescence|fluoresce]] (or glow) when examined using a microarray scanner.
TheIncreased glowor decreased fluorescense intensity indicates that cells in the sample hadhave recently transcribed,or ceased transcription, of a gene that containedcontains the probed sequence ("recently," because cells tend to degrade RNAs soon after transcribing them). The intensity of the glowfluorescense dependsis onroughly howproportional manyto the number of copies of a particular mRNA that were present and thus roughly indicates the ''activity'' or ''expression level'' of that gene. So arrays in aArrays sensecan paint a picture or "profile" of which genes in the [[genome]] are active in a particular cell type and under a particular condition.
Because mostmany proteins remainhave of unknown functionfunctions, and because many genes are active all the time in all kinds of cells, researchers usually use microarrays to make close comparisons between similar cell types. For example, an RNA sample from [[brain tumor]] cells, might be compared to a sample from healthy [[neuron]]s or [[glia]]. Probes that bind RNA in the tumor sample but not in the healthy one may indicate genes that are uniquely associated with the disease. Typically in such a test, the two sample's cDNAs are tagged with two distinct colors, enabling comparison on a single chip. Researchers hope to find molecules that couldcan be therapeutically targeted for treatment with drugs among the various [[protein]]s encoded by disease-associated genes.
Although the chips detect RNAs andthat may or may not be translated into active proteins, many scientists refer to these kinds of analysis as [[gene expression|"expression analysis"]] or [[expression profiling]]. Since there are hundreds ofor thousands of distinct probes on an array, each microarray experiment can accomplish the equivalent of thousands of genetic tests in parallel. Arrays have therefore dramatically accelerated many types of investigations.
DependingMicroarrays onare thealso technologybeing used to fabricateidentify thegenetic chips,mutations microarraysand mayvariation alsoin individuals and across populations. Short oligonucleotide arrays can be used into identifyingindentify hereditarythe single nucleotide polymorphisms (SNPs) that are thought to be responsible for genetic mutationsvariation and variationthe insource individualsof andsusceptibility acrossto populationsgenetically caused diseases. Generally termed "genotyping" applications, chips may be used in this fashion for forensic applications, rapidly discovering or measuring genetic predisposition to disease, andor identifying DNA-based drug candidates.
The lack of standardization in non-commercial arrays presents an [[interoperability problem]] in [[bioinformatics]], which hinders the exchange of array data. Many researchers use Affymetrix technology to a large extent because it is popular and standardized which can simplify the comparison of results from different laboratories. At the same time, various grass-roots [[open source|open-source]] projects are attempting to facilitate the exchange and analysis of data produced with non-proprietary chips. The MIAME (Minimal Information About a Microarray Experiment) standard for describing a microarray experiment is being adopted by many [[Scientific journal|journals]] as a requirement for the submission of papers based on microarray results.
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