High-Throughput SNP Genotyping by SBE/SBH

  • Ion I. Măndoiu
  • Claudia Prăjescu
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3992)


Despite much progress over the past decade, current Single Nucleotide Polymorphism (SNP) genotyping technologies still offer an insufficient degree of multiplexing when required to handle user-selected sets of SNPs. In this paper we propose a new genotyping assay architecture combining multiplexed solution-phase single-base extension (SBE) reactions with sequencing by hybridization (SBH) using universal DNA arrays such as all k-mer arrays. Our contributions include a study of multiplexing algorithms for SBE/SBH genotyping assays and preliminary experimental results showing the achievable multiplexing rates. Simulation results on datasets both randomly generated and extracted from the NCBI dbSNP database suggest that the SBE/SBH architecture provides a flexible and cost-effective alternative to genotyping assays currently used in the industry, enabling genotyping of up to hundreds of thousands of user-specified SNPs per assay.


Single Nucleotide Polymorphism Genotyping Assay Single Nucleotide Polymorphism Genotyping Array Probe Single Nucleotide Polymorphism Locus 
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  1. 1.
    Sharan, R., Gramm, J., Yakhini, Z., Ben-Dor, A.: Multiplexing schemes for generic SNP genotyping assays. Journal of Computational Biology 12(5), 514–533 (2005)CrossRefGoogle Scholar
  2. 2.
    Tonisson, N., Kurg, A., Lohmussaar, E., Metspalu, A.: Arrayed primer extension on the DNA chip - method and application. In: Schena, M. (ed.) Microarray Biochip Technology, pp. 247–263. Eaton Publishing (2000)Google Scholar
  3. 3.
    Hubbell, E.: Multiplex sequencing by hybridization. Journal of Computational Biology 8(2), 141–149 (2001)CrossRefGoogle Scholar
  4. 4.
    Naef, F., Magnasco, M.: Solving the riddle of the bright mismatches: Labeling and effective binding in oligonucleotide arrays. Physical Review E 68, 11906–11910 (2003)CrossRefGoogle Scholar
  5. 5.
    Măndoiu, I., Prăjescu, C., Trincă, D.: Improved tag set design and multiplexing algorithms for universal arrays. In: Priami, C., Zelikovsky, A. (eds.) Transactions on Computational Systems Biology II. LNCS (LNBI), vol. 3680, pp. 124–137. Springer, Heidelberg (2005)CrossRefGoogle Scholar
  6. 6.
    Măndoiu, I., Prăjescu, C.: High-throughput SNP genotyping by SBE/SBH. ACM Computing Research Repository, cs.DS/0512052 (2005)Google Scholar
  7. 7.
    Duckworth, W., Manlove, D., Zito, M.: On the approximability of the maximum induced matching problem. Journal of Discrete Algorithms 3, 79–91 (2005)MathSciNetzbMATHCrossRefGoogle Scholar
  8. 8.
    Wallace, R., Shaffer, J., Murphy, R., Bonner, J., Hirose, T., Itakura, K.: Hybridization of synthetic oligodeoxyribonucleotides to phi chi 174 DNA: the effect of single base pair mismatch. Nucleic Acids Res. 6(11), 6353–6357 (1979)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Ion I. Măndoiu
    • 1
  • Claudia Prăjescu
    • 1
  1. 1.Computer Science & Engineering DepartmentUniversity of ConnecticutStorrsUSA

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