ABSTRACT
Hundreds of disease susceptibility genes have been identified to date. It has become evident that useful genetic profiling depends on having the capability to analyze large numbers of polymorphic sites distributed widely throughout the genome (Schafer and Hawkins, 1998). A number of technical approaches to this
type of polymorphic analysis have been developed. These include such techniques as polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP) analysis; microsatellite marker PCR with products gel-resolved; allele-specific oligonucleotide (ASO) PCR with the detection specificity built into either a primer or a polymorphism specific hybridizing oligonucleotide; single-strand conformation polymorphism (SSCP) analysis; denaturing gradient gel electrophoresis (DGGE); chemical or enzymatic mismatch cleavage (CCM); and direct Sanger sequencing (Hall et al., 1996; Mifflin, 1996; McKenzie et al., 1998). However, throughput for all of these techniques saturates too quickly to accommodate the high level of parallel analysis required for executing broad genetic profiling efficiently. DNA oligonucleotide microarrays stand out among the numerous technical innovations that have been generated to address this problem. These two-dimensional collec tions of immobilized DNA sequences offer the option of performing large numbers of genetic analyses in parallel using hybridization-based assays. Their success has made them one of the most popular approaches to performing highly parallel genetic analysis (Marshall and Hodgson, 1998; Ramsay, 1998).
