Microarrays pp 121-138 | Cite as

Genotyping Arrays

  • Michael J. Lodes
  • Dominic Suciu
  • David Danley
  • Andrew McShea
Part of the Integrated Analytical Systems book series (ANASYS)


Although the most common use of DNA microarrays is gene expression profiling, microarrays are also used for many other applications, including genotyping, resequencing, SNP analysis, and DNA methylation assays. Here we describe genotyping arrays for Influenza A subtype identification and for upper respiratory pathogen diagnostics using standard hybridization techniques and we also describe resequencing, SNP, and methylation assays using an enzyme-based strategy [25, 26].


Ataxia Telangiectasia Mutate Ataxia Telangiectasia Sodium Metabisulphite Single Nucleotide Polymorphism Assay Sequence Reconstruction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Jodi Dalrymple and Marty Ross for their contributions to this study.


  1. 1.
    Fouchier R.A., V. Munster, A. Wallensten, T.M. Bestebroer, S. Herfst, D. Smith, G.F. Rimmelzwaan, B. Olsen, and A.D. Osterhaus. (2005) Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J. Virol. 79(5), 2814–2822.CrossRefGoogle Scholar
  2. 2.
    Scholtissek, C., H. Burger, O. Kistner, and K.F. Shortridge. (1985) The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses. Virology. 147(2), 287–294.CrossRefGoogle Scholar
  3. 3.
    Mizuta, K., N. Katsushima, S. Ito, K. Sanjoh, T. Murata, C. Abiko, and S. Murayama. (2003) A rare appearance of influenza A(H1N2) as a reassortant in a community such as Yamagata where A(H1N1) and A(H3N2) co-circulate. Microbiol. Immunol. 47(5), 359–361.Google Scholar
  4. 4.
    Webby, R.J, and R.G. Webster. (2001) Emergence of influenza A viruses. Phil. Trans. R. Soc. Lond. B356, 1815–1826.Google Scholar
  5. 5.
    Allwinn, R., W. Preiser, H. Rabenau, S. Buxboum, M. Sturmer, and H.W. Doerr. (2002) Laboratory diagnosis of influenza–Virology or serology? Med. Microbiol. Immunol. (Berl) 191(3–4), 157–160.Google Scholar
  6. 6.
    Amano, Y., and Q. Cheng. (2005) Detection of influenza virus: Traditional approaches and development of biosensors. Anal. Bioanal. Chem. 381(1), 156–184.CrossRefGoogle Scholar
  7. 7.
    Palmer D.F., M.T. Coleman, W.R. Dowdle, and G.C. Schild. (1975) Advanced laboratory techniques for influenza diagnosis. Immunology Series No. 6. U.S. Department of Health, Education, and Welfare. p. 51–52.Google Scholar
  8. 8.
    Ueda, M., A. Maeda, N. Nakagawa, T. Kase, R. Kubota, H. Takakura, A. Ohshima, and Y. Okuno. (1998) Application of subtype-specific monoclonal antibodies for rapid detection and identification of influenza A and B viruses. J. Clin. Microbiol. 36(2), 340–344.Google Scholar
  9. 9.
    Ellis, J.S., and M.C. Zambon. (2002) Molecular diagnosis of influenza. Rev. Med. Virol. 12(6), 375–389.CrossRefGoogle Scholar
  10. 10.
    Korimbocus J., N. Scaramozzino, B. Lacroix, J.M. Crance, D. Garin, and G. Vernet. (2005) DNA probe array for the simultaneous identification of herpes viruses, enteroviruses, and flaviviruses. J. Clin. Microbiol. 43(8), 3779–3787.CrossRefGoogle Scholar
  11. 11.
    Schweiger, B., I. Zadow, and R. Heckler. (2002) Antigenic drift and variability of influenza viruses. Med. Microbiol. Immunol. (Berl). 191(3–4), 133–138.Google Scholar
  12. 12.
    Taubenberger, J.K., and S.P. Layne. (2001) Diagnosis of influenza virus: Coming to grips with the molecular era. Mol. Diagn. 6(4), 291–305.Google Scholar
  13. 13.
    Wang, D., L. Coscoy, M. Zylberberg, P.C. Avila, H.A. Boushey, D. Ganem, and J.L. DeRisi. (2002) Microarray-based detection and genotyping of viral pathogens. PNAS. 99(4), 15687–15692.CrossRefGoogle Scholar
  14. 14.
    Zou, S. (1997) A practical approach to genetic screening for influenza virus variants. J. Clin. Microbiol. 35(10), 2623–2627.Google Scholar
  15. 15.
    Adeyefa, C.A., K. Quayle, and J.W. McCauley. (1994) A rapid method for the analysis of influenza virus genes: Application to the reassortment of equine influenza virus genes. Virus. Res. 32(3), 391–399.CrossRefGoogle Scholar
  16. 16.
    Hoffmann, E., J. Stech, Y. Guan, R.G. Webster, and D.R. Perez. (2001) Universal primer set for the full-length amplification of all influenza A viruses. Arch. Virol. 146, 1–15.CrossRefGoogle Scholar
  17. 17.
    Bodrossy, L., and A. Sessitsch. (2004) Oligonucleotide microarrays in microbial diagnosis. Curr. Opin. Microbiol. 7(3), 245–254.CrossRefGoogle Scholar
  18. 17.
    Templeton, K.E., S.A. Scheltinga, M.F.C. Beersma, A.C.M. Kroes, and E.C.J. Claas. (2004) Rapid and sensitive method using multiplex real-time PCR for diagnosis of infections by influenza A and influenza B viruses, respiratory syncytial virus, and parainfluenza viruses 1, 2, 3, and 4. J. Clin. Microbiol. 42(4), 1564–1569.CrossRefGoogle Scholar
  19. 18.
    Baxi, M.K., S. Baxi, A. Clavijo, K.M. Burton, and D. Deregt. (2006) Microarray-based detection and typing of foot-and-mouth disease virus. Vet. J. 172(3):473–481.CrossRefGoogle Scholar
  20. 19.
    Ivshina, A.V., G.M. Vodeiko, V.A. Kuznetsov, D. Volokhov, R. Taffs, V.I. Chizhikov, R.A. Levandowski, and K.M. Chumakov. (2004) Mapping of genomic segments of influenza B virus strains by an oligonucleotide microarray method. J. Clin. Microbiol. 42(12), 5793–5801.CrossRefGoogle Scholar
  21. 20.
    Kessler N., O. Ferraris, K. Palmer, W. Marsh, and A. Steel. (2004) Use of the DNA flow-thru chip, a three-dimensional biochip, for typing and subtyping of influenza viruses. J. Clin. Microbiol. 42(5), 2173–2185.CrossRefGoogle Scholar
  22. 21.
    Li, J., S. Chen, and D.H. Evans. (2001) Typing and subtyping influenza virus using DNA microarrays and multiplex reverse transcriptase PCR. J. Clin. Microbiol. 39(2), 696–704.CrossRefGoogle Scholar
  23. 22.
    Sengupta, S., K. Onodera, A. Lai, and U. Melcher. (2003) Molecular detection and identification of influenza viruses by oligonucleotide microarray hybridization. J. Clin. Microbiol. 41(10), 4542–4550.CrossRefGoogle Scholar
  24. 23.
    Wang, D., A. Urisman, Y.-T. Liu, M. Springer, T.G. Ksiazek, D.D. Erdman, E.R. Mardis, M. Hickenbotham, V. Magrini, J. Eldred, J.P. Latreille, R.K. Wilson, D. Ganem, and J.L. DeRisi. (2003) Viral discovery and sequence recovery using DNA microarrays. PLoS Biol. 1(2), 257–260.CrossRefGoogle Scholar
  25. 24.
    Roth, S.B., J. Jalava, O. Ruuskanen, A. Ruohola, and S. Nikkari. (2004) Use of an oligo-nucleotide array for laboratory diagnosis of bacteria responsible for acute upper respiratory infections. J. Clin. Microbiol. 42 (9), 4268–4274.CrossRefGoogle Scholar
  26. 25.
    Lodes, M.J., D. Suciu, M. Elliott, A.G. Stover, M. Ross, M. Caraballo, K. Dix, J. Crye, R.J. Webby, W.J. Lyon, D.L. Danley, and A. McShea. (2006) Use of semiconductor-based oligo-nucleotide microarrays for influenza A virus subtype identification and sequencing. J. Clin. Microbiol. 44(4), 1209–1218.CrossRefGoogle Scholar
  27. 26.
    Lodes, M.J., D. Suciu, J.L. Wilmoth, M. Ross, K. Dix, K. Bernards, A.G. Stöver, M. Quintana, N. Iihoshi, W.J. Lyon, D.L. Danley, and A. McShea. (2007) Identification of upper respiratory tract pathogens using electrochemical detection on an oligonucleotide microarray. PLoS ONE. 2(9), e924.CrossRefGoogle Scholar
  28. 27.
    Dill, K., D.D. Montgomery, A.L. Ghindilis, K.R. Schwarzkopf, S.R. Ragsdase, and A.V. Oleinikov. (2004) Immunoassays based on electrochemical detection using microelectrode arrays. Biosens. Bioelectron. 20, 736–742.CrossRefGoogle Scholar
  29. 28.
    Ghindilis, A.L., Smith, M.W., Schwarzkopf, K.R., Roth, K., Peyvan, K., Munro, S., Lodes, M.J., Stover, A., Bernards, K., Dill, K., and McShea, A. (2007) CombiMatrix oligonucle-otide arrays: Genotyping and gene expression assays employing electrochemical detection. Biosens. Bioelectron. 22(9–10):1853–1860.CrossRefGoogle Scholar
  30. 29.
    Liu, R.H., M.J. Lodes, T. Nguyen, T. Siuda, M. Slota, H.S. Fuji, and A. McShea. (2006) Validation ao a fully integrated microfluidic array device for influenza A subtype identification and sequencing. Anal. Chem. 2006 Jun 15; 78(12), 4184–4193.CrossRefGoogle Scholar
  31. 30.
    Macken, C., H. Lu, J. Goodman, and L. Boykin. (2001) The value of a database in surveillance and vaccine selection. in Options for the Control of Influenza IV. A.D.M.E. Osterhaus, N. Cox, and A.W. Hampson (Eds.). Amsterdam: Elsevier Science, 2001, 103–106.Google Scholar
  32. 31.
    Yuen, K.Y. and S.S.Y. Wong. (2005) Human infection by avian influenza A H5N1. Hong Kong Med. J. 11(3), 189–199.Google Scholar
  33. 32.
    Helio, T., L. Halme, M. Lappalainen, H. Fodstad, P. Paavola-Sakki, U. Turunen, M. Farkkila, T. Krusius, and K. Kontula. (2003) CARD15/NOD2 gene variants are associated with famil-ially occurring and complicated forms of Crohn's disease. Gut. 52(4), 558–562.CrossRefGoogle Scholar
  34. 33.
    Newman, B., M.S. Silverberg, X. Gu, Q. Zhang, A. Lazaro, A.H. Steinhart, G.R. Greenberg, A.M. Griffiths, R.S. McLeod, Z. Cohen, M. Fernandez-Vina, C.I. Amos, and K. Siminovitch. (2004) CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease. Am. J. Gastroenterol. 99(2), 306–315.CrossRefGoogle Scholar
  35. 34.
    Brant, S.R., C.I. Panhuysen, D. Nicolae, D.M. Reddy, D.K. Bonen, R. Karaliukas, L. Zhang, E. Swanson, L.W. Datta, T. Moran, G. Ravenhill, R.H. Duerr, J.P. Achkar, A.S. Karban, and J.H. Cho. (2003) MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am. J. Hum. Genet. 73(6), 1282–1292.CrossRefGoogle Scholar
  36. 35.
    Fang, N.Y., T.C. Greiner, D.D. Weisenburger, W.C. Chan, J.M. Vose, L.M. Smith, J.O. Armitage, R.A. Mayer, B.L. Pike, F.S. Collins, and J.G. Hacia. (2003) Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma. PNAS. 100(9), 5372–5377.CrossRefGoogle Scholar
  37. 36.
    Hacia, J.G., B. Sun, N. Hunt, K. Edgemon, D. Mosbrook, C. Robbins, S.P.A. Fodor, D.A. Tagle, and F.S. Collins (1998) Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays. Genome Res. 8, 1245–1258.Google Scholar
  38. 37.
    Kirk, B.W., M. Feinsod, R. Favis, R.M. Kliman, and F. Barany, (2002) Single nucleotide polymorphism seeking long-term association with complex diseases. Nucleic Acids Res. 30(15), 3295–3311.CrossRefGoogle Scholar
  39. 38.
    Kwok, P.-Y. (2001) Methods for genotyping single nucleotide polymorphisms. Annu. Rev. Genomics Hum. Genet. 2, 235–258.CrossRefGoogle Scholar
  40. 39.
    Jenkins, S., and N. Gibson. (2002) High-throughput SNP genotyping. Comp. Funct. Genom. 3, 57–66.CrossRefGoogle Scholar
  41. 40.
    Shi, M.M. (2001) Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies. Clin. Chem. 47(2), 164–172.Google Scholar
  42. 41.
    Hacia, J.G. (1999) Resequencing and mutational analysis using oligonucleotide microarrays. Nature Genetics. Supplement 21, 42–47.CrossRefGoogle Scholar
  43. 42.
    Urakawa, H., S. El Fantroussi, H. Smidt, J.C. Smoot, E.H. Tribou, J.J. Kelly, P.A. Noble, and D.A. Stahl. (2003) Optimization of single-base-pair mismatch discrimination in oligonucle-otide microarrays. Appl. Environ. Microbiol. 69(5), 2848–2856.CrossRefGoogle Scholar
  44. 43.
    Patil, N., A.J. Berno, D.A. Hinds, W.A. Barrett, J.M. Doshi, C.R. Hacker, C.R. Kautzer, D.H. Lee, C. Marjoribanks, D.P. McDonough, B.T. Nguyen, M.C. Norris, J.B. Sheehan, N. Shen, D. Stern, R.P. Stokowski, D.J. Thomas, M.O. Trulson, K.R. Vyas, K.A. Frazer, S.P. Fodor, and D.R. Cox. (2001) Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21. Science. 294, 1719–1723.CrossRefGoogle Scholar
  45. 44.
    Broude, N.E., T. Sano, C.L. Smith, and C.R. Cantor. (1994) Enhanced DNA sequencing by hybridization. PNAS. 91, 3072–3076.CrossRefGoogle Scholar
  46. 45.
    Dubiley S, E. Kirillov, and A. Mirzabekov. (1999) Polymorphism analysis and gene detection by minisequencing on an array of gel-immobilized primers. PNAS. 27(18), e19.Google Scholar
  47. 46.
    O'Meara, D., A. Ahmadian, J. Odeberg, and J. Lundeberg. (2002) SNP typing by apyrase-mediated allele-specific primer extension on DNA microarrays. NAR. 30(15), e75.CrossRefGoogle Scholar
  48. 47.
    Rickert, A.M., T.A. Borodina, E.J. Kuhn, H. Lehrach, and S. Sperling. (2004) Refinement of single-nucleotide polymorphism genotyping methods on human genomic DNA: Amplifluor allele-specific polymerase chain reaction versus ligation detection reaction-TaqMan. Anal. Biochem. 330(2), 288–297.CrossRefGoogle Scholar
  49. 48.
    Zhong, X-b., R. Reynolds, J.R. Kidd, K.K. Kidd, R. Jenison, R.A. Marlar, and D.C. Ward. (2003) Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips. PNAS. 100(20), 11559–11564.CrossRefGoogle Scholar
  50. 49.
    Iannone, MA., J.D. Taylor, J. Chen, M.S. Li, P. Rivers, K.A. Slentz-Kesler, and M.P. Weiner. (2000) Multiplexed single nucleotide polymorphism genotyping by oligonucleotide ligation and flow cytometry. Cytometry. 39(2), 131–140.CrossRefGoogle Scholar
  51. 50.
    Chen, X., K.J. Livak, and P.-Y. Kwok. (1998) A homogeneous, ligase-mediated DNA diagnostic test. Genome Res. 8, 549–556.Google Scholar
  52. 51.
    Consolandi, C., A. Frosini, C. Pera, G.B. Ferrara, R. Bordoni, B., Castiglioni, E. Rizzi, A. Mezzelani, L.R. Bernardi, G. DeBellis, and C. Battaglia. 2004. Polymorphism analysis within the HLA-A locus by universal oligonucleotide array. Hum. Mutat. 24(5), 428–434.CrossRefGoogle Scholar
  53. 52.
    Chen, H., G. Deng, Z. Li, G. Tian, Y. Li, P. Jiao, L. Zhang, Z. Liu, R.G. Webster, and K.Yu. (2004) The evolution of H5N1 influenza viruses in ducks in southern China. PNAS. 101(28), 10452–10457.CrossRefGoogle Scholar
  54. 53.
    Lee, C-W., D.E. Swayne, J.A. Linares, D.A. Senne, and E.L. Suarez, (2005) H5N2 Avian influenza outbreak in Texas. J. Virol. 79(17), 11412–11421.CrossRefGoogle Scholar
  55. 54.
    Cooper, G.M. (2000) The Cell: A Molecular Approach. Second edition, Boston University. Sinauer Associates, Sunderland, MA.Google Scholar
  56. 55.
    Schumacher A., P. Kapranov, Z. Kaminsky, J. Flanagan, A. Assadzadeh, P. Yau, C. Virtanen, N. Winegarden, J. Cheng, T. Gingeras, and A. Petronis. (2006) Microarray-based DNA meth-ylation profiling: Technology and applications. Nucleic Acids Res. 34(2), 528–542.CrossRefGoogle Scholar
  57. 56.
    Gebhard C., L. Schwarzfischer, T.H. Pham, E. Schilling, M. Klug, R. Andreesen, and M. Rehli. (2006) Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia. Cancer Res. 66(12), 6118–6128.CrossRefGoogle Scholar
  58. 57.
    Lewin, J., A.O. Schmitt, P. Adorjan, T. Hildmann, and C. Piepenbrock. (2004) Quantitative DNA methylation analysis based on four-dye trace data from direct sequencing of PCR amplificates. Bioinformatics. 20(17), 3005–3012.CrossRefGoogle Scholar
  59. 58.
    Galm O., J.G. Herman, and S.B. Baylin. (2006) The fundamental role of epigenetics in hemat-opoietic malignancies. Blood Rev.. 20(1), 1–13.CrossRefGoogle Scholar
  60. 59.
    Adrien L.R., N.F. Schlecht, N. Kawachi, R.V. Smith, M. Brandwein-Gensler, A. Massimi, S. Chen, M.B. Prystowsky, G. Childs, and T.J. Belbin. (2006) Classification of DNA meth-ylation patterns in tumor cell genomes using a CpG island microarray. Cytogenet Genome Res. 114(1), 16–23.CrossRefGoogle Scholar
  61. 60.
    Yan P.S., C.M. Chen, H. Shi, F. Rahmatpanah, S.H. Wei, and T.H. Huang. (2002) Applications of CpG island microarrays for high-throughput analysis of DNA methylation. J. Nutr. 132(8 Suppl), 2430S–2434S.Google Scholar
  62. 61.
    Hatada, I., M. Fukasawa, M. Kimura, S. Morita, K. Yamada, T. Yoshikawa, S. Yamanaka, C. Endo, A. Sakurada, M. Sato, T. Kondo, A. Horii, T. Ushijima, and H. Sasaki. (2006) Genome-wide profiling of promoter methylation in human. Oncogene. 25(21), 3059–3064.CrossRefGoogle Scholar
  63. 62.
    Paulin R., G.W. Grigg, M.W. Davey, and A.A. Piper. (1998) Urea improves efficiency of bisulphite-mediated sequencing of 5'-methylcytosine in genomic DNA. Nucleic Acids Res. 26(21), 5009–5010.CrossRefGoogle Scholar
  64. 63.
    Rein, T., H. Zorbas, and M. DePamphilis. (1997) Active mammalian replication origins are associated with a high-density cluster of mCpG dinucleotides. Mol. Cell Biol. 17, 416–426.Google Scholar
  65. 64.
    Clark, S.J., J. Harrison, C.L. Paul, and M. Frommer, (1994) High sensitivity mapping of methylated cytosines. Nucleic Acids Res., 22, 2990–2997.CrossRefGoogle Scholar
  66. 65.
    Lipatov, A.S., E.A. Govorkova, R.J. Webby, H. Ozaki, M. Peiris, Y. Guan, L. Poon, and R.G. Webster. (2004) Influenza: Emergence and control. J. Virol. 78(17), 8951–8959.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michael J. Lodes
    • 1
  • Dominic Suciu
    • 1
  • David Danley
    • 1
  • Andrew McShea
    • 1
  1. 1.CombiMatrix Corp.MukilteoWA

Personalised recommendations