Direct detection of point mutations by mismatch analysis: application to haemophilia B

Nucleic Acids Res. 1989 May 11;17(9):3347-58. doi: 10.1093/nar/17.9.3347.


Rapid detection of point mutations in genomic DNA has been achieved by chemical mismatch analysis of heteroduplexes formed between amplified wild-type and target sequences in the human factor IX gene. Amplification and mismatch detection (AMD) analysis of DNA from relatives of haemophilia B patients permitted carrier diagnosis by direct identification of the presence or absence of the mutation in all cases, thus eliminating the need for the informative segregation of polymorphic markers. This extends diagnostic capability to virtually all haemophilia B families. AMD analysis permits detection of all sequence variations in genomic DNA and is therefore applicable to direct diagnosis of X-linked and autosomal diseases and for identification of new polymorphisms for genetic mapping.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Composition
  • Base Sequence
  • Cattle
  • DNA / genetics*
  • Factor IX / genetics
  • Factor VII / genetics
  • Factor X / genetics
  • Genes
  • Genetic Carrier Screening
  • Hemophilia A / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Heteroduplexes / genetics
  • Oligonucleotide Probes
  • Protein C / genetics
  • Prothrombin / genetics


  • Nucleic Acid Heteroduplexes
  • Oligonucleotide Probes
  • Protein C
  • Factor VII
  • Prothrombin
  • Factor IX
  • Factor X
  • DNA