title: 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.
authors: ICI Diagnostics, Northwich, Cheshire, UK.
authors: C R
authors: CR
authors: Newton
authors: A
authors: A
authors: Graham
authors: L E
authors: LE
authors: Heptinstall
authors: S J
authors: SJ
authors: Powell
authors: C
authors: C
authors: Summers
authors: N
authors: N
authors: Kalsheker
authors: J C
authors: JC
authors: Smith
authors: A F
authors: AF
authors: Markham
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis / Q000379:methods; D004259:DNA-Directed DNA Polymerase; D005784:Gene Amplification; D006580:Genetic Carrier Screening / Q000379:methods; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019914:Taq Polymerase; D013698:Templates, Genetic; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000515:alpha 1-Antitrypsin; D019914:Taq Polymerase; D004259:DNA-Directed DNA Polymerase