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Polymerase chain reaction

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Summary

The PCR, like recombinant DNA technology, has had an enormous impact in both basic and diagnostic aspects of molecular biology because it can produce large amounts of a specific DNA fragment from small amounts of a complex template. Recombinant DNA techniques create molecular clones by conferring on a specific sequence the ability to replicate by inserting it into a vector and introducing the vector into a host cell. PCR represents a form of “in vitro cloning” that can generate, as well as modify, DNA fragments of defined length and sequence in a simple automated reaction. In addition to its many applications in basic molecular biological research, PCR promises to play a critical role in the identification of medically important sequences as well as an important diagnostic one in their detection.

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References

  1. Mullis KB, Faloona F: Specific synthesis of DNA in vitro via a polymerase catalysed chain reaction. Meth Enzymol 155:335–350, 1987

    Google Scholar 

  2. Saiki R, Scharf S, Faloona F, Mullis K, Horn G, Erlich HA, Arnheim N: Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354, 1985

    Google Scholar 

  3. Saiki RK, Gelfand DH, Stoffel S, Scharf S, Higuchi RH, Horn GT, Mullis KB, Erlich HA: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491, 1988

    Google Scholar 

  4. Scharf SJ, Horn GT, Erlich HA: Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science 223:1076–1078, 1986

    Google Scholar 

  5. Jeffreys AJ, Wilson V, Newmann R, Keyte J: Amplification of human minisatellites by the polymerase chain reaction: Towards DNA fingerprinting of single cells. Nucleic Acids Res 16:10953–10971, 1988

    Google Scholar 

  6. Fucharoen S, Fucharoen G, Fucharoen P, Fukumaki Y: A novel ochre mutation in the β-thalassemia gene of a Thai. J Biol Chem 264:7780–7783, 1987

    Google Scholar 

  7. Tindall KR, Kunkel TA: Fidelity of DNA synthesis by theThermus aquaticus DNA polymerase. Biochemistry 27:6008–6013, 1988

    Google Scholar 

  8. Gelfand D:Taq DNA polymerase.In PCR Technology: Principles and Applications of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 17–22

    Google Scholar 

  9. Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA: Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes. Nature 324:163–166, 1986

    Google Scholar 

  10. Bugawan TL, Saiki RK, Levenson CH, Watson RM, Erlich HA: The use of non-radioactive oligonucleotide probes to analyze enzymatically amplified DNA for prenatal diagnosis and forensic HLA typing. Bio/Technology 6:943–947, 1988

    Google Scholar 

  11. Li H, Gyllensten UB, Cui X, Saiki RK, Erlich HA, Arnheim N: Amplification and analysis of DNA sequences in single human sperm and diploid cells. Nature 335:414–417, 1988

    Google Scholar 

  12. Lench N, Stanier P, Williamson R: Simple non-invasive method to obtain DNA for gene analysis. Lancet 2:1356–1358, 1987

    Google Scholar 

  13. Shibata DK, Martin JW, Arnheim N: Analysis of DNA sequences in forty-year-old paraffin-embedded thin-tissue sections: A bridge between molecular biology and classical histology. Cancer Res 48:4564–4566, 1988

    Google Scholar 

  14. Higuchi R, von Beroldingen CH, Sensabaugh GF, Erlich HA: DNA typing from single hairs. Nature 332:543–546, 1988

    Google Scholar 

  15. Wrischnik LA, Higuchi RG, Stoneking M, Erlich HA, Arnheim N, Wilson AC: Length mutations in human mitochondrial DNA: Direct sequencing of enzymatically amplified DNA. Nucleic Acids Res 15:529–542, 1987

    Google Scholar 

  16. Wong C, Dowling CE, Saiki RK, Higuchi RG, Erlich HA, Kazazian HH Jr: Characterization of beta-thalassemia mutations using direct genomic sequencing of amplified single copy DNA. Nature 330:384–386, 1987

    Google Scholar 

  17. Higuchi R, Krummel B, Saiki RK: A general method of in vitro preparation and specific mutagenesis of DNA fragments: Study of protein and DNA interaction. Nucleic Acids Res 16:7351–7367, 1988

    Google Scholar 

  18. Fischer SG, Lerman LS: DNA fragments differing by single case-pair substitutions are separated in denaturing gradient gels: Correspondence with melting theory. Proc Natl Acad Sci USA 80:1579–1584, 1983

    Google Scholar 

  19. Sheffield VC, Cox DR, Lerman LS, Myers RM: Attachment of a 40-base-pair G+C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. Proc Natl Acad Sci USA 86:232–236, 1989

    Google Scholar 

  20. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554, 1988

    Google Scholar 

  21. Cotton RG, Rodriguez NR, Campbell RD: Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci USA 85:4397–4401, 1988

    Google Scholar 

  22. Trainer GL, Hobbs FW, Livak KJ, Kornher S, Johnson PR, Jensen MA, Korolkoff PN: New methods for labeling nucleic acids with reported groups. J Cell Biochem S13E:289, 1989

    Google Scholar 

  23. Kogan SC, Doherty M, Gitschier J: An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A. N Engl J Med 317:985–990, 1987

    Google Scholar 

  24. Horn GT, Richards B, Klinger KW: Amplification of a highly polymorphic VNTR segment by the polymerase chain reaction. Nucleic Acids Res 17:2140, 1989

    Google Scholar 

  25. Weber JL, May PE: Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388–396, 1989

    Google Scholar 

  26. Rappolee AD, Mark D, Banda MJ, Werb Z: Wound macrophages express TGF-alpha and other growth factorsin vivo: Analysis by mRNA phenotyping. Science 241:708–712, 1988

    Google Scholar 

  27. Gilliland G, Perrin S, Franklin H: Quantitative amplification of mRNA using polymerase chain reaction. J Cell Biochem S13E:270, 1989

    Google Scholar 

  28. Sarkar G, Sommer S: Access to a messenger RNA sequence or its protein product is not limited by tissue or species specificity. Science 244:331–334, 1989

    Google Scholar 

  29. Kinzler KW, Vogelstein B: Whole genome PCR: application to the identification of sequences bound by gene regulatory proteins. Nucleic Acids Res 17:3645–3653, 1989

    Google Scholar 

  30. Loh EY, Elliott JF, Cwirla S, Lanier LL, Davis MM: Polymerase chain reaction with single-sided specificity: Analysis of T cell receptor delta chain. Science 243:217–220, 1989

    Google Scholar 

  31. Frohman MA, Duch MK, Martin GR: Rapid production of full-length cDNAs from rare transcripts: Amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci USA 85:8998–9002, 1988

    Google Scholar 

  32. Shyamala V, Ames GF: A procedure for rapid genome walking by polymerase chain reaction. J Cell Biochem SBE:306, 1989

    Google Scholar 

  33. Acha-Orbea H, Mitchell DJ, Timmermann L, Wraith DC, Tausch GS, Waldor MK, Zamvil SS, McDevitt HO, Steinman L: Limited heterogeneity of T-cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54:263–273, 1988

    Google Scholar 

  34. Urban JL, Kumar V, Kono DH, Gomez C, Horvath SJ, Clayton J, Ando DG, Sercarz EE, Hood L: Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 54:577–592, 1988

    Google Scholar 

  35. Lee CC, Wu XW, Gibbs RA, Cook RG, Muzny DM, Caskey CT: Generation of cDNA probes directed by amino acid sequence: Cloning of urate oxidase. Science 239:1288–1291, 1988

    Google Scholar 

  36. Mack DH, Sninsky JJ: A sensitive method for the identification of uncharacterized viruses related to known virus groups: hepadnavirus model system. Proc Natl Acad Sci USA 85:6977–6981, 1988

    Google Scholar 

  37. Ludecke HJ, Senger G, Claussen U, Horsthemke B: Cloning defined regions of the human genome by microdissection of banded chromosomes and enzymatic amplification. Nature 338:348–350, 1989

    Google Scholar 

  38. Nelson DL, Caskey CT:Alu PCR: The use of repeat sequence primers for amplification of human DNA from complex sources.In PCR Technology: Applications and Principles of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 113–118

    Google Scholar 

  39. Triglia T, Peterson MG, Kemp DJ: A procedure forin vitro amplification of DNA segments that lie outside the boundaries of known sequences. Nucleic Acids Res 16:8186, 1988

    Google Scholar 

  40. Ochman H, Gerber AS, Hartl DL: Genetic applications of an inverse polymerase chain reaction. Genetics 120:621–623, 1988

    Google Scholar 

  41. Doetschman T, Maeda N, Smithies O: Targeted mutation of theHprt gene in mouse embryonic stem cells. Proc Natl Acad Sci USA 85:8583–8587, 1988

    Google Scholar 

  42. Kocher TD, White TJ: Evolutionary analysis via PCR.In PCR Technology: Applications and Principles of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 137–147

    Google Scholar 

  43. Embury SH, Scharf SJ, Saiki RK, Gholson MA, Golbus M, Arnheim N, Erlich HA: Rapid prenatal diagnosis of sickle cell anemia by a new method of DNA analysis. N Engl J Med 316:656, 1987

    Google Scholar 

  44. Saiki RK, Chang CA, Levenson CH, Warren TC, Boehm CD, Kazazian HH Jr, Erlich HA: Diagnosis of sickle cell anemia and β-thalassemia with enzymatically amplified DNA and nonradioactive allele-specific oligonucleotide probes. N Engl J Med 319:537–541, 1988

    Google Scholar 

  45. DiLella AG, Marvit J, Lidsky AS, Guttler F, Woo SLC: An amino-acid substitution involved in phenylkeonuria is in linkage disequilibrium with DNA haplotype 2. Nature 327:333–336, 1987

    Google Scholar 

  46. Kazazian HH Jr: Use of PCR in the diagnosis of monogenic disease.In PCR Technology: Applications and Principles of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 153–169

    Google Scholar 

  47. Gitschier J, Wood WI, Tuddenham EGD, Shuman MA, Goralka TM, Chen EY, Lawn RM: Detection and sequence of mutations in the factor VIII gene of haemophiliacs. Nature 315:427–430, 1985

    Google Scholar 

  48. Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT: Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 16:11141–11156, 1988

    Google Scholar 

  49. Feldman G, Williamsen R, Beaudet A, O'Brien W: Prenatal diagnosis of cystic fibrosis by DNA amplification for detection of KM-19 polymorphism. Lancet 2:102–103, 1988

    Google Scholar 

  50. Riordan JR, Rommens JH, Kereus B, Alon N, Rozmabel R, Grzelczak G, Zielenski J, Lok S, Plavsic N, Chou J, Drumm ML, Lannuzzi MC, Collins FS, Tsui L: Identification of the cystic fibrosis gene: Cloning and characterization of complementary, DNA. Science 245:1066–1072, 1989

    Google Scholar 

  51. Saiki R, Walsh PS, Levenson CH, Erlich HA: Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci USA (in press), 1989

  52. Erlich HA, Bugawan TL: HLA class II gene polymorphism: DNA typing, evolution, and relationship to disease susceptibility.In PCR Technology: Applications and Principles of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 193–208

    Google Scholar 

  53. Scharf SJ, Friedmann A, Brautbar C, Szafer F, Steinman L, Horn G, Gyllensten U, Erlich HA: HLA class II allelic variation and susceptibility toPemphigus vulgaris. Proc Natl Acad Sci USA 85:3504–3508, 1988

    Google Scholar 

  54. Scharf SJ, Friedmann A, Steinman L, Brautbar C, Erlich HA: Specific HLA-DQß and DRßI alleles confer susceptibility toPemphigus vulgaris. Proc Natl Acad Sci USA 86:6215–6219, 1989

    Google Scholar 

  55. Todd JA, Bell JI, McDevitt HO: HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329:599–604, 1987

    Google Scholar 

  56. Horn GT, Bugawan TL, Long C, Erlich HA: Allelic sequence variation of the HLA-DQ loci: Relationship to serology and insulin-dependent diabetes susceptibility. Proc Natl Acad Sci USA 85:6012–6016, 1988

    Google Scholar 

  57. Sinha AA, Brautbar C, Szafer F, Friedmann A, Tzfoni E, Todd JA, Bell JI, McDevitt HO: A newly characterized HLA-DQ beta allele associated withPemphigus vulgaris. Science 239:1026–1029, 1988

    Google Scholar 

  58. Bugawan T, Angelini G, Larrick J, Auricchio S, Ferrara GB, Erlich HA: A combination of a particular HLA-DPß allele and HLA-DQ heterodimer confers susceptibility to coeliac disease. Nature 339:470–473, 1989

    Google Scholar 

  59. Kagnoff MF, Harwood JI, Bugwan TL, Erlich HA: Structural analysis of the HLA-DR, -DQ, and -DP alleles on the celiac disease-associated HLA-DR3 (DRw17) haplotype. Proc Natl Acad Sci USA 86:6274–6278, 1989

    Google Scholar 

  60. Begovich A, Bugawan TL, Nepom, Klitz W, Nepom, Erlich HA: A specific HLA-DPß allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis. Proc Natl Acad Sci USA (in press), 1989

  61. Erlich HA, Gelfand D, Saiki RK: Specific DNA amplification. Nature 331:461–462, 1988

    Google Scholar 

  62. Bos J: Detection ofras oncogenes using PCR.In PCR Technology: Applications and Principles of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 225–233

    Google Scholar 

  63. Crescenzi M, Seto M, Herzig GP, Weiss PD, Griffith RC, Korsmeyer SJ: Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease. Proc Natl Acad Sci USA 85:4869–4873, 1988

    Google Scholar 

  64. Kawasaki ES, Clark SS, Coyne MY, Smith SD, Champlin R, Witte ON, McCormick FP: Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemiaspecific mRNA sequences amplified in vitro. Proc Natl Acad Sci USA 85:5698–5702, 1988

    Google Scholar 

  65. Lee MS, Chang KS, Freireich EJ, Kantarjian HM, Talpaz M, Trujillo JM, Stass SA: Detection and minimal residual bcr/abl transcripts by a modified polymerase chain reaction. Blood 72:893–897, 1988

    Google Scholar 

  66. Price CM, Rassool S, Shivji, MKK, Gow J, Tew CJ, Haworth C, Goldman JM, Wiedemann LM: Rearrangement of the breakpoint cluster region and expression of P210 BCR-ABL in a “masked” Philadelphia chromosome-positive acute myeloid leukemia. Blood 72:1829–1832, 1988

    Google Scholar 

  67. Dobrovic A, Trainor J, Morley AA: Detection of the molecular abnormality in chronic myeloid leukemia by use of the polymerase chain reaction. Blood 72:2063–2065, 1988

    Google Scholar 

  68. Hermans A, Selleri L, Gow J, Grosveld GC: Absence of alternative splicing in ber-abl mRNA in chronic myeloid leukemia cell lines. Blood 72:2066–2069, 1988

    Google Scholar 

  69. Knudson A Jr: Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 45:1437–1447, 1985

    Google Scholar 

  70. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Presisinger AC, Jessup JM, van Tuinen P, Ledbetter DH, Barker, Nakamura Y, White R, Vogelstein B: Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221, 1989

    Google Scholar 

  71. Cavanee W, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie B, Murphree A, Strong L, White RL: Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–785, 1983

    Google Scholar 

  72. Vogelstein B, Fearon ER, Kern SE, Hamilton SR, Preisinger AC, Nakamura Y, White R: Allelotype of colorectal carcinomas. Science 244:207–211, 1989

    Google Scholar 

  73. Kwok S, Sninsky J: Application of PCR to the detection of human infectious diseases.In PCR Technology: Applications and Principles of DNA Amplification, H Erlich (ed). New York, Stockton Press, 1989, pp 235–244

    Google Scholar 

  74. Kwok S, Mack DH, Mulis KB, Poiesz B, Ehrlich G, Blair D, Friedman-Kien A, Sninsky JJ: Identification of human immunodeficiency virus sequences by usingin vitro enzymatic amplification and oligomer cleavage detection. J Virol 61:1690–1694, 1987

    Google Scholar 

  75. Rayfield M, DeCock K, Heyward W, Goldstein L, Krebs J, Kwok S, Lee S, McCormick J, Moreau MM, Odehouri K, Schochetman G, Sninsky J, Ou CY: Mixed human immunodeficiency virus (HIV) infection in an individual: Demonstration of both HIV type 1 and type 2 proviral sequences by using polymerase chain reaction. J Infect Dis 158:1170–1176, 1988

    Google Scholar 

  76. Bhagavati S, Ehrlich G, Kula RW, Kwok S, Sninsky J, Udani V, Poiesz BJ: Detection of human T-cell lymphoma/leukemia virus type I DNA and antigen in spiral fluid and blood of patients with chronic progressive myelopathy. N Engl J Med 318:1141–1147, 1988

    Google Scholar 

  77. Larzul D, Guigue F, Sninsky JJ, Mack DH, Brechot C, Guesdon JL: Detection of hepatitis B virus sequences in serum by usingin vitro enzymatic amplification J Virol Methods 20:227–237, 1988

    Google Scholar 

  78. Shibata D, Martin WJ, Appleman MD, Causey DM, Leedom JM, Arnheim N: Detection of cytomegalovirus DNA in peripheral blood of patients infected with human immunodeficiency virus. J Infect Dis 158:1185–1192, 1988

    Google Scholar 

  79. Shibata DK, Arnheim N, Martin WJ: Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction. J Exp Med 167:225–230, 1988

    Google Scholar 

  80. Manos MM, Ting Y, Wright DK, Lewis AJ, Broker TR, Wolinsky SM: The use of polymerase chain reaction amplification for the detection of genital human papillomaviruses.In Cancer Cells, Vol. 7, Molecular Diagnostics of Human Cancer. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, pp 209–214

  81. Steffan RS, Atlas RM: DNA amplification to enhance detection of genetically engineered bacteria in environmental samples. Appl Environ Microbiol 54:2185–2191, 1988

    Google Scholar 

  82. Lyonnet S, Caillaud C, Rey F, Berthelon M, Frezal J, Rey J, Munnich A: Guthrie cards for detection of point mutations in phenylketonuria. Lancet 2:507–508, 1988

    Google Scholar 

  83. Williams C, Weber L, Williamson R, Hjelm M: Gutherie spots for DNA-based carrier testing in cystic fibrosis. Lancet 2:693–694, 1988

    Google Scholar 

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  1. Department of Human Genetics, Cetus Corporation, 1400 53rd Street, 94608, Emeryville, California

    Henry A. Erlich

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Erlich, H.A. Polymerase chain reaction. J Clin Immunol 9, 437–447 (1989). https://doi.org/10.1007/BF00918012

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