Sequencing by Hybridization is a class of methods for determining the order in which nucleotides occur on a strand of DNA. Typically used for looking for small changes relative to a known DNA sequence. The binding of one strand of DNA to its complementary strand in the DNA double-helix (aka hybridization) is sensitive to even single-base mismatches when the hybrid region is short or is specialized mismatch detection proteins are present. This is exploited in a variety of ways, most notable via DNA chips or microarrays with thousands to billions of synthetic oligonucleotides found in a genome of interest plus many known variations or even all possible single-base variations.

This technology has largely been displaced by Sequencing-by-synthesis based methods.

Examples of commercial systems

• Affymetrix
• Complete Genomics Inc.

References

• Drmanac R et al. Sequencing by hybridization (SBH): advantages, achievements, and opportunities. Adv Biochem Eng Biotechnol. 2002;77:75-101. PMID 12227738
• Hanna GJ et al. Comparison of Sequencing by Hybridization and Cycle Sequencing for Genotyping of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. J Clin Microbiol. 2000 July; 38(7): 2715–2721. PMID 10878069

• Church, George M. Genomes for all. Scientific American. 2006 Jan;294(1):52. PMID 16468433

Also see: Sequencing by ligation