1989/01/01 by Charles R. Newton, Alexander Graham, Lesley Heptinstall +5 · 6 citations
Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #RNA and protein synthesis mechanisms #Molecular Biology Techniques and Applications
paper · doi:10.1093/nar/17.7.2503
openalex publication_date 1989/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
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.