High-throughput SNP genotyping with the Masscode system

QIAGEN Genomics, Inc, has developed the Masscode tagging system for DNA lab eling and detection. In this application, the Masscode system is described as applied to high-throughput single-nucleotide polymorphism (SNP) genotypi ng. The labeling system is based on a small-moleculal-weight tag that is co valently attached through a photocleavable linker to a DNA oligonucleotide. The tagged oligonucleotide is used as a primer in an allele-specific PCR S NP discrimination assay. The allele-spscific amplicons are differentiated t hrough their Masscode tag assignments. After a photolysis step to cleave th e tags from the amplicon, the samples are introduced into a single quadrupo le mass spectrometry detection system for analysis. Genotyping determinatio ns are based on the relative proportions of the paired allele tags. The sys tem has a lower limit of detection in the femtomolar range (10(-15) M). At present, 30 different Masscode tags may be used simultaneously in a multipl ex fashion to routinely provide more than 40,000 SNP genotyping measurement s daily. Further developments will allow for the simultaneous detection of several hundred tags.