High-Density Arrays and Insights into Genome function

Genome projects are producing sequence data at a very fast pace (http:// www.ncbi.nlni.nih.govlEntrez/Genomeforghtml). The discovery of the complete human genome sequence is only a few years away and a working draft with 90% coverage is promised to appear by the time of this publication (Strategy meeting on human genome sequencing, Cold Spring Harbor, 1999). In addition to the detailed sequence, biologists will receive a list of all 50-100,000 genes in the human genome and the challenge then turns towards organizing the genes and understanding how genes operate and interact to produce a living system. Traditional gene-by-gene analyses are inefficient for obtaining information about the function, regulation, and sequence variation of the thousands of genes in a genome. Highly parallel analyses are needed to be able to survey biology from a global perspective. One type of tool for studying biology from a global perspective is the high-density array, also known as a microarray, which consists of a miniaturized, high-density array of probes bound to a solid surface. Current applications have been based on DNA probes, although in theory other molecules such as proteins or small molecular weight compounds can also be arrayed at high density. Exploiting the specificity of hybridization, DNA probes on high-density arrays can detect the presence of individual target sequences in complex mixtures. This ability allows for massively parallel hybridization assays for large numbers of genes and sequences, and has been primarily applied to survey genomes for variations in mRNA expression levels or between DNA sequences. Using. high-density DNA arrays for mRNA expression studies, rapid, accurate, and