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 pr esent in an unknown DNA sequence. Computational approaches can then be used to assemble the complete sequence. As a validation of this conce pt, the sequences of three DNA fragments, 343 base pairs in length, we re determined with octamer oligonucleotides. Possible applications of SBH include physical mapping (ordering) of overlapping DNA clones, seq uence checking, DNA fingerprinting comparisons of normal and disease-c ausing genes, and the identification of DNA fragments with particular sequence motifs in complementary DNA and genomic libraries. The SBH te chniques may accelerate the mapping and sequencing phases of the human genome project.