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Published June 11, 1993 | public
Journal Article

DNA sequence determination by hybridization: a strategy for efficient large-scale sequencing


The concept of sequencing by hybridization (SBH) makes use of an array of all possible n-nucleotide oligomers (n-mers) to identify n-mers present in an unknown DNA sequence. Computational approaches can then be used to assemble the complete sequence. As a validation of this concept, the sequences of three DNA fragments, 343 base pairs in length, were determined with octamer oligonucleotides. Possible applications of SBH include physical mapping (ordering) of overlapping DNA clones, sequence checking, DNA fingerprinting comparisons of normal and disease-causing genes, and the identification of DNA fragments with particular sequence motifs in complementary DNA and genomic libraries. The SBH techniques may accelerate the mapping and sequencing phases of the human genome project.

Additional Information

© 1993 American Association for the Advancement of Science. 7 December 1992; Accepted 15 March 1993. We thank M. Stodolsky of the Department of Energy, Office of Health and Environmental Research, for monitoring the blind test and aiding in its design. Supported by U.S. Department of Energy, Office of Health and Environmental Research, under contract W-31-109-ENG-38.

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