Detection of polymorphisms at cytosine phosphoguanadine dinucleotides and diagnosis of haemophilia B carriers

Lancet. 1989 Mar 25;1(8639):631-4. doi: 10.1016/s0140-6736(89)92141-7.


The polymerase chain reaction procedure (PCR) was used to detect a polymorphic Hha I site adjacent to the factor IX locus in a panel of 33 phenotypically normal caucasian individuals. This technique was also applied to a haemophilia B family pedigree. The Hha I polymorphic site was located 8 kb 3' to the factor IX gene, and the proportion of female subjects expected to be heterozygous at this site was 0.48. The Hha I locus was in linkage equilibrium with the other polymorphic loci on the factor IX gene. These findings, besides increasing the proportion of caucasian individuals whose haemophilia B carrier state can be diagnosed from 79% to 89%, demonstrate this widely applicable use of PCR for the detection of DNA polymorphism at cytosine phosphoguanadine dinucleotides irrespective of the methylation status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • DNA-Directed DNA Polymerase
  • Dinucleoside Phosphates / genetics*
  • Factor IX / analysis
  • Factor IX / genetics
  • Genetic Carrier Screening*
  • Genetic Linkage
  • Genetic Markers
  • Genotype
  • Haplotypes
  • Hemophilia B / genetics*
  • Humans
  • Molecular Sequence Data
  • Pedigree
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Recombination, Genetic


  • Dinucleoside Phosphates
  • Genetic Markers
  • cytidylyl-3'-5'-guanosine
  • Factor IX
  • DNA-Directed DNA Polymerase