High-throughput polymorphism screening and genotyping with high-density oligonucleotide arrays

A highly reliable and efficient technology has been developed for high-thro ughput DNA polymorphism screening and large-scale genotyping. Photolithogra phic synthesis has been used to generate miniaturized, high-density oligonu cleotide arrays. Dedicated instrumentation and software have been developed for array hybridization, fluorescent detection, and data acquisition and a nalysis. Specific oligonucleotide probe arrays have been designed to rapidl y screen human STSs, known genes and full-length cDNAs. This has led to the identification of several thousand biallelic single-nucleotide polymorphis ms (SNPs). Meanwhile, a rapid and robust method has been developed for geno typing these SNPs using oligonucleotide arrays, Each allele of an SNP marke r is represented on the array by a set of perfect match and mismatch probes . Prototype genotyping chips have been produced to detect 400, 600 and 3000 of these SNPs. Based on the preliminary results, using oligonucleotide arr ays to genotype several thousand polymorphic loci simultaneously appears fe asible. (C) 1999 Elsevier Science B.V. All rights reserved.