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Nucleic Acids Res. Apr 11, 1989; 17(7): 2503–2516.
PMCID: PMC317639

Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS).

Abstract

We have improved the "polymerase chain reaction" (PCR) to permit rapid analysis of any known mutation in genomic DNA. We demonstrate a system, ARMS (Amplification Refractory Mutation System), that allows genotyping solely by inspection of reaction mixtures after agarose gel electrophoresis. The system is simple, reliable and non-isotopic. It will clearly distinguish heterozygotes at a locus from homozygotes for either allele. The system requires neither restriction enzyme digestion, allele-specific oligonucleotides as conventionally applied, nor the sequence analysis of PCR products. The basis of the invention is that unexpectedly, oligonucleotides with a mismatched 3'-residue will not function as primers in the PCR under appropriate conditions. We have analysed DNA from patients with alpha 1-antitrypsin (AAT) deficiency, from carriers of the disease and from normal individuals. Our findings are in complete agreement with allele assignments derived by direct sequencing of PCR products.

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Selected References

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  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Kan YW, Dozy AM. Antenatal diagnosis of sickle-cell anaemia by D.N.A. analysis of amniotic-fluid cells. Lancet. 1978 Oct 28;2(8096):910–912. [PubMed]
  • Solomon E, Bodmer WF. Evolution of sickle variant gene. Lancet. 1979 Apr 28;1(8122):923–923. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Newton CR, Kalsheker N, Graham A, Powell S, Gammack A, Riley J, Markham AF. Diagnosis of alpha 1-antitrypsin deficiency by enzymatic amplification of human genomic DNA and direct sequencing of polymerase chain reaction products. Nucleic Acids Res. 1988 Sep 12;16(17):8233–8243. [PMC free article] [PubMed]
  • Stoflet ES, Koeberl DD, Sarkar G, Sommer SS. Genomic amplification with transcript sequencing. Science. 1988 Jan 29;239(4839):491–494. [PubMed]
  • Engelke DR, Hoener PA, Collins FS. Direct sequencing of enzymatically amplified human genomic DNA. Proc Natl Acad Sci U S A. 1988 Jan;85(2):544–548. [PMC free article] [PubMed]
  • Petersen KB, Kølvraa S, Bolund L, Petersen GB, Koch J, Gregersen N. Detection of alpha 1-antitrypsin genotypes by analysis of amplified DNA sequences. Nucleic Acids Res. 1988 Jan 11;16(1):352–352. [PMC free article] [PubMed]
  • Chehab FF, Doherty M, Cai SP, Kan YW, Cooper S, Rubin EM. Detection of sickle cell anaemia and thalassaemias. Nature. 1987 Sep 24;329(6137):293–294. [PubMed]
  • 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. 1987 Oct 15;317(16):985–990. [PubMed]
  • Levinson B, Janco R, Phillips J, 3rd, Gitschier J. A novel missense mutation in the factor VIII gene identified by analysis of amplified hemophilia DNA sequences. Nucleic Acids Res. 1987 Dec 10;15(23):9797–9805. [PMC free article] [PubMed]
  • Wong C, Dowling CE, Saiki RK, Higuchi RG, Erlich HA, Kazazian HH., Jr Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Nature. 330(6146):384–386. [PubMed]
  • Conner BJ, Reyes AA, Morin C, Itakura K, Teplitz RL, Wallace RB. Detection of sickle cell beta S-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci U S A. 1983 Jan;80(1):278–282. [PMC free article] [PubMed]
  • Orkin SH, Markham AF, Kazazian HH., Jr Direct detection of the common Mediterranean beta-thalassemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis. J Clin Invest. 1983 Mar;71(3):775–779. [PMC free article] [PubMed]
  • Feldman GL, Williamson R, Beaudet AL, O'Brien WE. Prenatal diagnosis of cystic fibrosis by DNA amplification for detection of KM-19 polymorphism. Lancet. 1988 Jul 9;2(8602):102–102. [PubMed]
  • Williams C, Williamson R, Coutelle C, Loeffler F, Smith J, Ivinson A. Same-day, first-trimester antenatal diagnosis for cystic fibrosis by gene amplification. Lancet. 1988 Jul 9;2(8602):102–103. [PubMed]
  • Wong C, Antonarakis SE, Goff SC, Orkin SH, Boehm CD, Kazazian HH., Jr On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6529–6532. [PMC free article] [PubMed]
  • Estivill X, Farrall M, Scambler PJ, Bell GM, Hawley KM, Lench NJ, Bates GP, Kruyer HC, Frederick PA, Stanier P, et al. A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. Nature. 326(6116):840–845. [PubMed]
  • Farrall M, Estivill X, Williamson R. Indirect cystic fibrosis carrier detection. Lancet. 1987 Jul 18;2(8551):156–157. [PubMed]
  • Nukiwa T, Brantly M, Garver R, Paul L, Courtney M, LeCocq JP, Crystal RG. Evaluation of "at risk" alpha 1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes. J Clin Invest. 1986 Feb;77(2):528–537. [PMC free article] [PubMed]
  • Ludwig EH, Blackhart BD, Pierotti VR, Caiati L, Fortier C, Knott T, Scott J, Mahley RW, Levy-Wilson B, McCarthy BJ. DNA sequence of the human apolipoprotein B gene. DNA. 1987 Aug;6(4):363–372. [PubMed]
  • Chien A, Edgar DB, Trela JM. Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus. J Bacteriol. 1976 Sep;127(3):1550–1557. [PMC free article] [PubMed]
  • Long GL, Chandra T, Woo SL, Davie EW, Kurachi K. Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant. Biochemistry. 1984 Oct 9;23(21):4828–4837. [PubMed]
  • Tindall KR, Kunkel TA. Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase. Biochemistry. 1988 Aug 9;27(16):6008–6013. [PubMed]
  • Cooper DN, Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet. 1988 Feb;78(2):151–155. [PubMed]
  • Dermer SJ, Johnson EM. Rapid DNA analysis of alpha 1-antitrypsin deficiency: application of an improved method for amplifying mutated gene sequences. Lab Invest. 1988 Sep;59(3):403–408. [PubMed]

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