Sites of interest on the World Wide Web—edited by Rick Neubig

A Favorite Site for All Your Favorite Genes

With all of the genetic information available from the Human Genome Project, where do you turn to find comprehensive information about a particular gene or family of genes? Beyond the well-known Entrez System (http://www.ncbi.nlm.nih.gov/entrez/) to search PubMed or GenBank databases, you may find LocusLink (http://www.ncbi.nlm.nih.gov/LocusLink/) an even more useful tool for exploring the genes of mammals and other vertebrates. According to its home page, LocusLink “provides a single query interface to curated sequence and descriptive information about genetic loci.” This single source to sequences, annotations, and genetic variations (e.g., single nucleotide polymorphisms, or SNPs) is a great starting point for genetic investigations. Genes from human, mouse, rat, fruit fly, and zebrafish are all included, and the search interface makes it easy to limit your results to just one of these species.

You can search for standard terms such as “adrenergic receptor,” or by entering the name of a given gene family (e.g., ADR*). The codes for gene families are easy to learn by visiting the site. The article by Scotto and Johnson in this issue (pp 117–125) illustrates the use of such gene codes in its title pertaining to the MDR1 gene. A LocusLink query of MDR* yields thirty-eight loci of relevance to this clinically important gene, and a search on MDR1 will lead you to various information directly pertaining to the gene and the ATP-binding cassette protein that it encodes. This consistent searching convention makes gene family associations very apparent and much easier to deduce than in the chaotic naming of gene products in the GenBank database.

After entering a query, you will see a series of gene names followed by a row of colored letters, which will take you to information from the following databases: P, PubMed; O, OMIM (Online Mendelian Inheritance in Man); R, RefSeq (non-redundant sequence data); G, GenBank (sequence data, alternative format); P, protein sequence; H, HomoloGene; U, UniGene; and V, variation data (i.e., SNPs present in the public database). OMIM in particular is well annotated and gives a wealth of background about human genetic variations. The variation database, V, provides links to SNP information, which is of intense concern to the pharmacology of interindividual variation in drug response. With the rich set of resources available from the LocusLink starting point, it may become one of your main portals to genetic information.

Long QT Syndrome

Long QT syndrome arises from genetic alterations that have very important pharmacological implications. This genetic disease, caused by mutations in the genes that encode the subunits of potassium channels (see Abbott and Goldstein in this issue, pp 95–107), leads to life-threatening arrhythmias. These may be triggered or worsened by certain drugs. There are a number of excellent resources providing information about long QT syndrome, both for professionals (e.g., http://www.ncbi.nlm.nih.gov/disease/LQT.html) and the public at large (e.g., http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/longqt.html and http://www.sads.org/overview.html).

Chips and Maps: Microarray Gene Expression

A critical determinant of biological function and pharmacological responses is the expression of gene products. An incredibly powerful approach to study gene expression is the microarray technology developed by several groups of industrial and academic investigators. A general site that explains microarray methods and provides links to pertinent resources is posted at http://www.gene-chips.com. Analysis of such massive “gene chip” data requires powerful software tools. An intriguing new approach, called GenMAPP, has been developed by Bruce Conklin and colleagues at the Gladstone Institutes and the University of California at San Francisco. Free software for GenMAPP (version 1.0 beta) is currently available for Windows platforms (http://genmapp.org). With novel visual components, this software displays changes in expression of functionally related genes in the context of graphically displayed biochemical pathways. It also includes tools to prepare diagrams of cell structures (e.g., nucleus, Golgi apparatus, endoplasmic reticulum, and plasma membrane) as a framework for viewing changes in gene expression. The extent or time course of the changes is color coded. Although the number of genes that can be displayed in this manner is limited, the relations among genes for which the expression has changed are readily visible.