Skip to main content
SpringerLink
Log in

Electrophoretic Methods for Mutation Detection and DNA Sequencing

  • Chapter
Molecular Diagnostics

Abstract

Since its development in 1985, polymerase chain reaction (PCR) has revolutionized basic and applied research (1,2). In 1993, Mullis was awarded the Nobel Prize in Chemistry for the development of PCR. With DNA or cDNA as a template, millions of copies of a target sequence are generated during the reaction. Introduction of the thermophilic Thermus aquaticus polymerase increased the specificity of the reaction and made automation and routine use possible (3–5). The ability of PCR to produce multiple copies of a discrete portion of the genome has resulted in its incorporation into techniques used in a wide variety of research and clinical applications. An extraordinary range of clinical applications of PCR have emerged, including diagnosis of inherited disease, human leukocyte antigen (HLA) typing, identity testing, infectious disease diagnosis and management, hematologic disease diagnosis and staging, and susceptibility testing for cancer. The development of technically simple and reliable methods to detect sequence variations in specific genes is becoming more important as the number of genes associated with specific diseases grows. DNA sequencing is considered the “gold standard” for characterization of specific nucleotide alteration(s) that result in genetic disease. Although sequencing was long considered too cumbersome, expensive, and operator dependent for use in the clinical laboratory, a combination of clinical need and improved technology has brought automated DNA sequencing into routine clinical use. However, even though sequencing technology is now firmly entrenched in the clinical molecular diagnostics laboratory, it is still too expensive and time-consuming for all the laboratory’s mutation-detection needs. There are a number of PCR-based mutation-detection strategies that can be used to identify both characterized and uncharacterized mutations and sequence variations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Saiki, R. K., Scharf, S., Faloona, F., et al. Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354, 1985.

    Article  CAS  PubMed  Google Scholar 

  2. Mullis, K. B. and Faloona, F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 155:335–350, 1987.

    Article  CAS  PubMed  Google Scholar 

  3. Brock, T. D. and Freeze, H. Thermus aquaticus gen. n. and sp. n., a non-sporulating extreme thermophile. J. Bacteriol. 98:289–297, 1969.

    Article  CAS  PubMed  Google Scholar 

  4. Chien, A., Edgar, D. B. and Trela, J. M. Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus. J. Bacteriol. 127:1550–1557, 1976.

    CAS  PubMed  Google Scholar 

  5. Saiki, R. K., Gelfand, D. H., Stoffel, S., et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491, 1988.

    Article  CAS  PubMed  Google Scholar 

  6. FMC BioProducts Catalog 1995, Technical Applications, FMC Bio Products, p. 70.

    Google Scholar 

  7. Jorgenson, J. W. and Lucas, K. D. Capillary zone electrophoresis. Science 222:266–272, 1983.

    Article  CAS  PubMed  Google Scholar 

  8. Tiselius, A. A new apparatus for electrophoretic analysis of colloidal mixtures. Trans. Faraday Soc. 33:524, 1937.

    Article  CAS  Google Scholar 

  9. Oda, R. P. and Landers, J. P. Introduction to capillary electrophore-sis. in Handbook of Capillary Electrophoresis, Landers, J. P., ed., CRC, Boca Raton, FL, pp. 1–48, 1997.

    Google Scholar 

  10. Ruiz-Martinez, M. C., Berka, J., Belenkii, A., Foret, F., Miller, A. W., and Karger, B. L. DNA sequencing by capillary electrophoresis with replaceable linear polyacrylamide and laser-induced fluorescence detection. Anal. Chem. 65:2851–2858, 1993.

    Article  CAS  PubMed  Google Scholar 

  11. Albarghouthi, M. N. and Barron, A. E. Polymeric matrices for DNA sequencing by capillary electrophoresis. Electrophoresis 21: 4096–4111 2000.

    Article  CAS  PubMed  Google Scholar 

  12. Albarghouthi, M. N., Buchholz, B. A., Huiberts, P. J., Stein, T. M., and Barron, A. E. Poly-N-hydroxyethylacrylamide (polyDuramide): a novel, hydrophilic, self-coating polymer matrix for DNA sequencing by capillary electrophoresis. Electrophoresis 23:1429–1440, 2002.

    Article  CAS  PubMed  Google Scholar 

  13. Heller, C. Influence of polymer concentration and polymer composition on capillary electrophoresis of DNA, in Introduction to the Capillary Electrophoresis of Nucleic Acids: Volume 1, Mitchelson, K. R. and Cheng, J., Eds. Humana, Totowa, NJ, pp. 111–123, 2000.

    Chapter  Google Scholar 

  14. Chiari, M., Cretich, M., Damin, F., Ceriotto, L., and Consonni, R. New adsorbed coatings for capillary electrophoresis. Electrophoresis 21:909–916, 2000.

    Article  CAS  PubMed  Google Scholar 

  15. Orita, M., Suzuki, Y., Sekiya, T., and Hiayashi, K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5:874–879, 1989.

    Article  CAS  PubMed  Google Scholar 

  16. Hollstein, M., Sidransky, D., Vogelstein, B., and Harris, C. C. p53 mutations in human cancers. Science 253:49–53, 1991.

    Article  CAS  PubMed  Google Scholar 

  17. Levine, A. J., Momand, J., and Finlay, C. A. The p53 tumor suppressor gene. Nature 351:453–456, 1991.

    Article  CAS  PubMed  Google Scholar 

  18. Sheffield, V. C., Beck, J. S., Kwitek, A. E., Sandstrom, D. W., and Stone, E. M. The sensitivity of single-strand conformational polymorphism analysis for the detection of single base substitutions Genomics 16:325–332, 1993.

    Article  CAS  PubMed  Google Scholar 

  19. Myers, R. M., Lerman, L. S., and Maniatis, T. Saturation mutagen-esis of cloned DNA fragments. Science 229:242–247, 1985.

    Article  CAS  PubMed  Google Scholar 

  20. Highsmith, W. E., Jr., Nataraj, A. J., Jin, Q., et al. Use of DNA toolbox for the characterization of mutation scanning methods. II. Evaluation of single-strand conformation polymorphism analysis. Electrophoresis 20:1195–1203, 1999.

    Article  CAS  PubMed  Google Scholar 

  21. Lin-Goerke, J. Ye, S., and Highsmith, W. E. Effects of gel matrix on the sensitivity of SSCP analysis: a study of the effects of novel gel matrices, fragment size, GC content, and base alteration. Am. J. Hum. Genet. 55 (suppl.):A188, 1994.

    Google Scholar 

  22. Ravnik-Glavac, M., Glavac, D., and Dean, M. Sensitivity of SSCP and heteroduplex method for mutation detection in the cystic fibro-sis gene. Hum. Mol. Genet. 3:801–807, 1994.

    Article  CAS  PubMed  Google Scholar 

  23. Ren, J. High-throughput single-strand conformation polymorphism analysis by capillary electrophoresis. J. Chromatogr. B 741: 115–128, 2000.

    Article  CAS  Google Scholar 

  24. Kourkine, I. V., Hestekin, C. N., Buchholz, B., and Barron, A. E. High-throughput, high-sensitivity genetic mutation detection by tandem single-strand conformation polymorphism/heteroduplex analysis capillary array electrophoresis. Anal. Chem. 74: 2565– 2572, 2002.

    Article  CAS  PubMed  Google Scholar 

  25. Atha, D., Wentz, H. M., Morehead, H., Tian, J., and O’Connel, C. D. Detection of p53 point mutations by single strand conformation polymorphism: analysis by capillary electrophoresis. Electrophoresis 19:172–179; 1998.

    Article  CAS  PubMed  Google Scholar 

  26. Wentz, H. M., Ramachandra, S., O’Connell, C. D. and Atha, D. Identification of known p53 point mutations by capillary elec-trophoresis using unique mobility profiles in a blinded study. Mutat. Res. 382:121–132, 1998.

    Google Scholar 

  27. Higasa, K., Kukita, Y., Baba, S., and Hayashi, K. Software for machine-independent quantitative interpretation of SSCP in capillary array electrophoresis. BioTechniques 33:1342–1348, 2002.

    CAS  PubMed  Google Scholar 

  28. O’Connel, C. D., Atha, D., Oldenburg, M., et al. Detection of p53 gene mutations: analysis by single-strand conformation polymorphism and Cleavase fragment length polymorphism. Electrophoresis 20:1211–1223, 1999.

    Article  Google Scholar 

  29. Liechti-Gallati, S., Schnieder, V., Neeser, D., and Kraemer, R. Two buffer PAGE system-based SSCP/HD analysis: a general protocol for rapid and sensitive mutation screening in cystic fibrosis and any other human genetic disease. Eur. J. Hum. Genet. 7: 590–598, 1999.

    Article  CAS  PubMed  Google Scholar 

  30. Bhattacharyya, A. and Lilley, D. M. J. The contrasting structures of mismatched DNA sequences containing looped-out bases (bulges) and multiple mismatches (bubbles). Nucleic. Acids Res. 17: 6821–6840, 1989.

    Article  CAS  PubMed  Google Scholar 

  31. Keen, J., Lester, D., Inglehaern, C., Curtus, A., and Bhattacharaya, S. Improved detection of heteroduplexes on Hydrolink gels. Trends Genet. 7:5, 1991.

    Article  CAS  PubMed  Google Scholar 

  32. Molinari, R. J., Conners, M., and Shorr, R. G. Hydrolink gels for electrophoresis, in Advances in Electrophoresis, Volume 6, Chrambach, A., Dunn, M. J., and Radola, B. J., eds., VCH, New York, pp. 44–60, 1993.

    Google Scholar 

  33. Highsmith, W. E., Jr., Jin, Q., Nataraj, A. J., et al. Use of a DNA toolbox for the characterization of mutation scanning methods. I. Construction of the toolbox and evaluation of heteroduplex analysis. Electrophoresis 20:1186–1194, 1999.

    Article  CAS  PubMed  Google Scholar 

  34. Ganguly, A., Rock, M. J., and Prockop, D. J. Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes. Proc. Natl. Acad. Sci. USA 90:10325–10329, 1993.

    Article  CAS  PubMed  Google Scholar 

  35. Ganguly, A. An update on conformation sensitive gel electrophore-sis. Hum. Mutat. 19(4):334–342, 2002.

    Article  CAS  PubMed  Google Scholar 

  36. Calladine, C. R., Collins, C. M., Drew, H. R., and Mott, M. R. A study of the electrophoretic mobility of DNA in agarose and pol-yarylamide gels. J. Mole. Biol. 221:981–1005, 1991.

    Article  CAS  Google Scholar 

  37. Myers, R. M., Lumelsky, N., Lerman, L. S., and Maniatis, T. Detection of single base substitutions in total genomic DNA. Nature 313:495–498, 1985.

    Article  CAS  PubMed  Google Scholar 

  38. Lerman, L. S. and Silverstein, K. Computational simulation of DNA melting and its application to denaturing gradient gel electrophore-sis. Methods Enzymol. 155:482–501, 1987.

    Article  CAS  PubMed  Google Scholar 

  39. Abrams, E. S., Murdaugh, S. E., and Lerman, L. S. Comprehensive detection of single base changes in human genomic DNA using denaturing gradient gel electrophoresis and a GC clamp Genomics 7:463–475, 1990.

    Article  CAS  PubMed  Google Scholar 

  40. Saleeba, J. A., Ramus, S. J., and Cotton, R. G. H. Complete mutation detection using unlabeled chemical cleavage. Hum. Mutat. 1:63–69,1992.

    Article  CAS  PubMed  Google Scholar 

  41. Cotton, R. G. H. Cleavage of mismatched based using chemical reagents. in Mutation Detection: A Practical Approach, Cotton, R. G. H., Edkins, E., Forrest, S., eds. Oxford University Press, Oxford 1998.

    Google Scholar 

  42. Myers, R. M., Larin, Z., and Maniatis, T. Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA : DNA duplexes. Science 230:1242–1246, 1985.

    Article  CAS  PubMed  Google Scholar 

  43. Gibbs, R. A., and Caskey, C. T. Identification and localization of mutations at the Lesch–Nyhan locus by ribonuclease A cleavage. Science 236:303–305, 1987.

    Article  CAS  PubMed  Google Scholar 

  44. Marini, J. C., Lewis, M. B., Wang, Q., Chen, K. J. and Orrison, B. M. Serine for glycine substitutions in type I collagen in two cases of type IV osteogenesis imperfecta (OI). J. Biol. Chem. 268: 2667–2673, 1993.

    CAS  PubMed  Google Scholar 

  45. Forrester, K., Almoguera, C., Han, K., Grizzle, W. E. and Perucho, M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327:298–303, 1987.

    Article  CAS  PubMed  Google Scholar 

  46. Murthy, K. K., Shen, S. -H., and Banville D. a sensitive method for detection of mutations: A PCR-based RNase Protection assay. DNA Cell. Biol. 14:87–94, 1995.

    Article  CAS  PubMed  Google Scholar 

  47. Goldrick, M. M., Kimball, G. R., Liu, Q., Martin, L. A., Sommer, S. S., and Tseng, J. Y. NIRCA: a rapid robust method for screening for unknown point mutations. Biotechniques. 21:106–112, 1996.

    CAS  PubMed  Google Scholar 

  48. Yoshino, K., Nishigaki, K., and Husimi, Y. Temperature sweep gel electrophoresis: a simple method to detect point mutations. Nucleic Acids Res. 19:3153, 1991.

    Article  CAS  PubMed  Google Scholar 

  49. Wong, L. J., Liang, M. H., Kwon, H., Park, J., Bai, R. K., and Tan, D.J. Comprehensive scanning of the entire mitochondrial genome for mutations. Clin. Chem. 48:1901–1912, 2002.

    CAS  PubMed  Google Scholar 

  50. Cotton, R. G. H., Rodrigues, N. R., and Campbell, R. D. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxlamine and osmium tetoxide and its application to the study of mutations. Proc. Natl. Acad. Sci. USA 85:4397–4401, 1988.

    Article  CAS  PubMed  Google Scholar 

  51. Goldrick, M. M. RNase cleavage-based methods for mutation/SNP detection, past and present. Hum. Mutat. 18:190–204, 2001.

    Article  CAS  PubMed  Google Scholar 

  52. Kogan, S. C., Doherty, M., and Gitschier, J. An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. N. Engl. J. Med. 317:985–990, 1987.

    Article  CAS  PubMed  Google Scholar 

  53. Feldman, G. L., Williamson, R., Beaudet, A. L., and O’Brien, W. E. Prenatal diagnosis of cystic fibrosis by DNA amplification for detection of KM-19 polymorphism. Lancet 8602:102, 1988.

    Article  Google Scholar 

  54. Yuan, R. Structure and mechanism of multifunctional restriction endonucleases. Annu. Rev. Biochem. 50:285–315, 1981.

    Article  CAS  PubMed  Google Scholar 

  55. Highsmith, W. E., Burch, L. H., Zhou, Z., et al. Identification of a splice site mutation (2789 + 5G > A) associated with small amounts of normal cystic fibrosis transmembrane conductance regulator mRNA and mild cystic fibrosis. Hum. Mutat. 9:332–338, 1997.

    Article  CAS  PubMed  Google Scholar 

  56. Haliassos, A., Chomel, J. C., Tesson, L., et al. Modification of enzy-matically amplified DNA for the destruction of point mutations. Nucleic Acids Res. 17:3606, 1989.

    Article  CAS  PubMed  Google Scholar 

  57. Friedman, K. J., Highsmith, W. E., and Silverman, L. M. Detecting multiple cystic fibrosis mutations by polymerase chain reaction-mediated site-directed mutagenesis. Clin. Chem. 37:7531991.

    CAS  PubMed  Google Scholar 

  58. Gasparini, P., Bonizzato, A., Dognini, M., and Pignatti, P. F. Restriction site generating–polymerase chain reaction (RG-PCR) for the probeless detection of hidden genetic variation: application to the study of some common cystic fibrosis mutations. Mol. Cell. Probes 6:1–7, 1992.

    Article  CAS  PubMed  Google Scholar 

  59. Lindeman, R., Hu, S. P., Volpato, F., and Trent, R. J. Polymerase chain reaction (PCR) mutagenesis enabling rapid non-radioactive detection of common β-thalassaemia mutations in Mediterraneans. Br. J. Haematol. 78:100–104, 1991.

    Article  CAS  PubMed  Google Scholar 

  60. Maxam, A. M. and Gilbert W. A new method for sequencing DNA A new method for sequencing DNA. Proc. Natl. Acad. Sci. USA 74: 560–564, 1977.

    Article  Google Scholar 

  61. Sanger, F., Nicklen, S., and Coulson, A. R. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci USA 74: 5463–5467, 1977.

    Article  CAS  PubMed  Google Scholar 

  62. Franca, L. T. C., Carriho, E., and Kist, T. B. L. A review of DNA sequencing techniques. Qu. Rev. Biophys. 35:169–200, 2000.

    Google Scholar 

  63. Slatko, B. E., Albright, L. M., and Tabor, S. DNA sequencing: commentary. in Current Protocols in Molecular Biology, Ausubel, F. M., Brent, R., Kingston, R. E., et al., eds., Wiley, New York, pp. 7.4A. 19–7.4A.39, 1998.

    Google Scholar 

  64. Tabor, S. and Richardson, C. C. Selective oxidation of the exonucle-ase domain of the bacteriophage T7 DNA polymerase. J. Biol. Chem. 262:15,330–15,333, 1987.

    CAS  PubMed  Google Scholar 

  65. Tabor, S. and Richardson, C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc. Natl. Acad. Sci. USA 84:4767–4771, 1987.

    Article  CAS  PubMed  Google Scholar 

  66. Tabor, S. and Richardson, C. C. Effect of manganese ions on the incorporation of dideoxynucleotides by T7 DNA polymerase and E. coli DNA polymerase. Proc. Natl. Acad. Sci. USA 86:4076–4080, 1989.

    Article  CAS  PubMed  Google Scholar 

  67. Tabor, S. and Richardson, C. C. A single residue in DNA poly-merases of the Escherichia coli DNA polymerase I family is critical for distinguishing between deoxy and dideoxyribonucleotides. Proc. Natl. Acad. Sci. USA 92: 6339–6343, 1995.

    Article  CAS  PubMed  Google Scholar 

  68. Smith, L., Fung, S., Hunkapiller, M., Hunkapiller, T., and Hood, L. The synthesis of oligonucleotides containing an aliphatic amino group at the 5′ terminus: synthesis of fluorescent DNA primers for use in DNA sequnce analysis. Nucleic Acids Res. 13:2399–2412, 1985.

    Article  CAS  PubMed  Google Scholar 

  69. Smith, L., Sanders, J., Kaiser, R., et al. Fluorescence detection in automated DNA sequence analysis. Nature 321:674–679, 1986.

    Article  CAS  PubMed  Google Scholar 

  70. Ansorge, W., Sproat, B., Stegemann, J., Schwager, C., and Zenke, M. Automated DNA sequencing: ultrasensitive detection of fluorescence bands during electrophoresis. Nucleic Acids Res. 15: 4593–4602, 1987.

    Article  CAS  PubMed  Google Scholar 

  71. Ju, J., Ruan, C., Fuller, C. W., Glazer, A. N., and Mathies, R. A. Fluorescence energy transfer dye-labeled primers for DNA sequencing and analysis. Proc. Natl. Acad. Sci. USA 92:4347–4351, 1995.

    Article  CAS  PubMed  Google Scholar 

  72. Lee, L. G., Spurgeon, S. L., Heiner, C. R., et al. New energy transfer dyes for DNA sequencing. Nucleic Acids Res. 25:2816–2822, 1997.

    Article  CAS  PubMed  Google Scholar 

  73. Zakeri, H., Amparo, G., Chen, S. M., Spurgeon, S., and Kwok, P. Y. Peak height pattern in dichlororrhodamine and energy transfer dye terminator sequencing. BioTechniques 25:406–414, 1998.

    CAS  PubMed  Google Scholar 

  74. Rosenblum, B. B., Lee, L. G., Spurgeon, S. L., et al. New dye-labeled terminators for improved DNA sequence patterns. Nucleic Acids Res. 25:4500–4504, 1997.

    Article  CAS  PubMed  Google Scholar 

  75. Huang, X. C., Quesada, M. A., and Mathies, R. A. DNA sequencing using capillary array electrophoresis. Anal. Chem. 64:2149–2154, 1992.

    Article  CAS  PubMed  Google Scholar 

  76. Kambara, H. and Takahashi, S. Multiple-sheathflow capillary array DNA analyser. Nature 361:565–566, 1993.

    Article  CAS  PubMed  Google Scholar 

  77. Ueno, K. and Yeung, E. S. Simultaneous monitoring of DNA fragments separated by electrophoresis in a multiplexed array of 100 capillaries. Anal. Chem. 66:1424–1431, 1994.

    Article  CAS  Google Scholar 

  78. Carrilho, E. DNA sequencing by capillary array electrophoresis and microfabricated array systems. Electrophoresis 21:55–65, 2000.

    Article  CAS  PubMed  Google Scholar 

  79. Kheterpal, I. and Mathies, R. A. Capillary array electrophoresis. Anal. Chem. 71:A31–A37, 1999.

    Google Scholar 

  80. Ewing, B., Hillier, L., Wendl, M. C., and Green, P. Base-calling of automated sequencer traces using phred. I. Accuracy Assesment. Genome Res. 8:175–185, 1998.

    CAS  PubMed  Google Scholar 

  81. Lee, L. G., Connell, C. R., Woo, S. L., et al. DNA sequencing with dye-labeled terminators and T7 DNA polymerase: effect of dyes and dNTPs on incorporation of dye-terminators and probability analysis of termination fragments. Nucleic Acids Res. 20:694–699, 1992.

    Google Scholar 

  82. Ewing, B. and Green, P. Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res. 8:186–194, 1998.

    CAS  PubMed  Google Scholar 

  83. Richterich, P. Estimation of errors in “raw” DNA sequences: a validation study. Genome Res. 8:251–259, 1998.

    CAS  PubMed  Google Scholar 

  84. Wilson, J. W. Update on antiretroviral drug resistance testing: combining laboratory technology with patient care. AIDS Reader 13: 25–30, 2003.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Laboratory Genetics, Department of Laboratory Medicine Pathology, Mayo Clinic, Rochester, MN

    W. Edward Highsmith Jr PhD

Authors
  1. W. Edward Highsmith Jr PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    William B. Coleman

  2. Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Gregory J. Tsongalis

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Highsmith, W.E. (2006). Electrophoretic Methods for Mutation Detection and DNA Sequencing. In: Coleman, W.B., Tsongalis, G.J. (eds) Molecular Diagnostics. Humana Press. https://doi.org/10.1385/1-59259-928-1:085

Download citation

  • DOI: https://doi.org/10.1385/1-59259-928-1:085

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-356-5

  • Online ISBN: 978-1-59259-928-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation