Sequencing by hybridization

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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.[1] The binding of one strand of DNA to its complementary strand in the DNA double-helix (known as hybridization) is sensitive to even single-base mismatches when the hybrid region is short or if specialized mismatch detection proteins are present. This is exploited in a variety of ways, most notably 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.[2][3]

The type of sequencing by hybridization described above has largely been displaced by other methods, including sequencing by synthesis, and sequencing by ligation (as well as pore-based methods). However hybridization of oligonucleotides is still used in some sequencing schemes, including hybridization-assisted pore-based sequencing, and reversible hybridization.[4]

Examples of commercial systems[edit]

  • Affymetrix (true sequencing-by-hybridization)
  • NABsys (Hybridization-assisted pore-based sequencing)
  • Complete Genomics Inc. (reversible-hybridization of probes that call-out a single base with each hybridization)

See also[edit]


  1. ^ Drmanac, R; et al. (2002). "Sequencing by hybridization (SBH): advantages, achievements, and opportunities". Adv Biochem Eng Biotechnol. 77: 75–101. PMID 12227738.
  2. ^ Preparata, FP; Upfal, E (2000). "Sequencing-by-hybridization at the information-theory bound: an optimal algorithm". J Comput Biol. 7 (3): 621–30. doi:10.1089/106652700750050970. PMID 11108482.
  3. ^ Hanna, GJ; et al. (July 2000). "Comparison of Sequencing by Hybridization and Cycle Sequencing for Genotyping of Human Immunodeficiency Virus Type 1 Reverse Transcriptase". J Clin Microbiol. 38 (7): 2715–2721. PMC 87006. PMID 10878069.
  4. ^ Church, George M. (January 2006). "Genomes for all". Scientific American. 294 (1): 52. doi:10.1038/scientificamerican0106-46. PMID 16468433.