With pending completion of the human genome project, a wealth of genetic information is rapidly becoming available. Application of this knowledge to medicine requires development of new techniques to monitor gene expression and rapidly evaluate genes for mutations and other sequence variations. Oligonucleotide arrays have shown great promise for these applications. Such arrays consist of a number of gene-specific Oligonucleotide probes immobilized at specific sites on a solid matrix. (Chip). Arrays can contain thousands of unique probe molecules, each fixed within an “address”. Gene chips can then be treated with labeled target nucleic acids (DNA or RNA) derived from cells of an organism. Hybridization of the targets with complementary probe sequences allows for immobilization of the label at specific sites on the chip. In this way, the presence of specific sequences can be determined and the amount of labeled target hybridized to a site can be quantitated, allowing for determination of amount of each target in a sample.
Use of DNA arrays to analyze sequences has led to detection of mutations in human cells. For example, high-density DNA arrays with thousands of Oligonucleotides probe have been used to screen for mutations that lead to ataxia telangiectasia, a recessive genetic disease characterized by neurological disorders, recurrent respiration infections, and dilated blood vessels in the skin and eyes. Similar studies have examined mutations in the hereditary breast and ovarian cancer gene BRCAI and other genetic markers for disease. In the future, such techniques may be developed into diagnostics for rapid screening of genomic DNA for disease-associated mutations.