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

Nucleic Acids Res. 1989 Apr 11;17(7):2503-16. doi: 10.1093/nar/17.7.2503.


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.

MeSH terms

  • Base Sequence*
  • DNA Mutational Analysis* / methods
  • DNA-Directed DNA Polymerase
  • Gene Amplification*
  • Genetic Carrier Screening / methods
  • Homozygote
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Taq Polymerase
  • Templates, Genetic
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency


  • alpha 1-Antitrypsin
  • Taq Polymerase
  • DNA-Directed DNA Polymerase