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Biologists often use two terms to describe alternative approaches for conducting experiments. "In vitro" (Latin for "in glass") refers to experiments typically carried out in test tubes with purified biochemicals. "In vivo" ("in life") experiments are performed directly on living organisms. In recent years, the indispensable use of computers and the Internet for genetic and molecular biology research has introduced a new term into the language: "in silico" ("in silicon"), referring to the silicon used to manufacture computer chips. In silico genetics experiments are those that are performed with a computer, often involving analysis of DNA or protein sequences over the Internet.

Geneticists and molecular biologists use the Internet much the same way most people do, communicating data and results through e-mail and discussion groups and sharing information on Web sites, for instance. They also make wide use of powerful Internet-based databases and analytical tools. Researchers are determining the DNA sequences of entire genomes at an ever accelerating pace, and are devising methods for cataloging entire sets of proteins (termed "proteomes") expressed in organisms. The databases to store all this information are growing at an equal pace, and the computer tools to sort through all the data are becoming increasingly sophisticated.

One of the most important Web sites for biological computer analysis (sometimes called bioinformatics) is that of the National Center for Biotechnology Information (NCBI), a part of the National Library of Medicine, which, in turn, is part of the National Institutes of Health. The NCBI Web site hosts DNA and protein sequence databases, protein three-dimensional structure databases, scientific literature databases, and search engines for retrieving files of interest. All of these resources are freely accessible to anyone on the Internet.

Of all the powerful analytical tools available at NCBI, probably the most important and heavily used is a set of computer programs called BLAST, for Basic Local Alignment Search Tool. BLAST can rapidly search many sequence databases to see whether any DNA or protein sequence (a "query sequence," supplied by the user) is similar to other sequences. Since sequence similarity usually suggests that two proteins or DNA molecules are homologous (i.e., that they are evolutionarily related and therefore may have—or encode proteins—with similar functions), discovering a blast match between an unknown protein or nucleic acid sequence and a well-characterized sequence provides an immediate clue about the function of the unknown sequence. An important scientific discovery that, in the past, may have taken many years of in vitro and in vivo analysis to arrive at is now made in a few seconds, with this simple in silico experiment.

Paul J. Muhlrad

Bibliography

Internet Resources

Basic Local Alignment Search Tool. National Center for Biotechnology Information. <http://www.ncbi.nlm.nih.gov/BLAST/>.

Baxevanis, Andreas D. "The Molecular Biology Database Collection: 2002 Update." Nucleic Acids Research. Oxford University Press. <http://www3.oup.co.uk/nar/database/>.

ExPASy Molecular Biology Server. Swiss Institute of Bioinformatics. <http://ca.expasy.org/>.

Virtual Library of Genetics. U.S. Department of Energy. <http://www.ornl.gov/TechResources/Human_Genome/genetics.html>.

Wellcome Trust Sanger Institute. <http://www.sanger.ac.uk/>.

WWW Virtual Library: Model Organisms. George Manning. <http://ceolas.org/VL/mo/>.

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