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sequencing by hybridization

A proposed approach to rapid sequencing of genomic DNA. The key tool for analysis is a superchip, a surface over which are attached at minute yet identifiable positions unlabelled oligonucleotide probes. For example, if pentanucleotides are used, there will be 625 (54) rows of unique pentanucleotides. The entire surface of the superchip is exposed to an amplified sample of the test DNA plus a ligase. Each unlabelled probe will hybridize to the DNA where there is a complementary sequence. The superchip is then overlaid by another chip that contains a similar array of rows of labelled oligonucleotides, but with the rows running across the rows of unlabelled probes. Where the labelled and unlabelled probes are complementary to adjacent sequences (in the example, a decanucleotide sequence), the ligase can join them and thus fix the label to the superchip. A robotic reader will identify the positions on the superchip that have become labelled and that therefore indicate the presence of a particular (decanucleotide) sequence. The overlap of the identified sequences will allow reconstruction of the entire sequence of the test DNA.

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Bridge the gap between chemically synthesized oligos and bological applications.

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