A new polymorphism in the human factor VIII gene: implications for linkage analysis in haemophilia A and for the evolution of int22h sequences

Br J Haematol. 2000 Nov;111(2):544-8. doi: 10.1046/j.1365-2141.2000.02373.x.


A new polymorphism in the human factor VIII gene has been localized and characterized. It is a biallelic, single nucleotide polymorphism located in intron 22 of the gene, within the 9.5 kb int22h-1 segment. The allelic forms are G (frequency 0.65) and A (frequency 0.35), giving a predicted rate of heterozygosity of 0.46. The polymorphism occurs within a CG dinucleotide and affects an MspI site (CCGG). Int22h-1 is duplicated twice extragenically at Xq28; both extragenic copies (int22h-2 and -3) are also polymorphic with respect to MspI. Investigation of 156 MspI [-] alleles, comprising 30 intragenic and 126 extragenic sites, indicated that all were due to A alleles and none had arisen by C to T transition within the CG dinucleotide. The intragenic MspI site (designated MspI A) is located 737 bases downstream of a previously described XbaI restriction fragment length polymorphism. Despite their close proximity, the polymorphisms are not in complete linkage disequilibrium; haplotype analysis in 85 factor VIII genes from a Caucasian population predicts an informativity of approximately 60% in linkage studies using both, compared with an informativity of approximately 47% in studies using either on its own.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Mapping*
  • Evolution, Molecular
  • Factor VIII / genetics*
  • Gene Frequency
  • Genetic Carrier Screening
  • Genotype
  • Hemophilia A / diagnosis
  • Hemophilia A / genetics*
  • Humans
  • Introns
  • Male
  • Polymorphism, Single Nucleotide*
  • Wales


  • Factor VIII