Factor VIII gene haplotypes and linkage disequilibrium for the indirect genetic analysis of hemophilia A in India

Clin Appl Thromb Hemost. 2009 May-Jun;15(3):334-9. doi: 10.1177/1076029607308872. Epub 2007 Dec 26.

Abstract

Genomic consequences of factor VIII gene haplotypes for the indirect genetic analysis of haemophilia A has not been done in India hitherto. Consequently, BclI/intron18, HindIII/intron 19, and XbaI/intron 22 restriction sites were investigated in 159 individuals from 42 families with hemophilia A. The frequencies of haplotype II, IV, VI, that is, BclI (+)-HindIII (-)- XbaI (+), BclI (+)HindIII (+)-XbaI (-), and BclI (-)-HindIII (-)-XbaI (+) were 0.312, 0.198, and 0.164 respectively. The high heterogeneity of haplotype II highlighted its potential for indirect genetic diagnosis of factor VIII. Analysis revealed strong but incomplete linkage disequilibrium (D' = 0.76, 0.68, and 0.51) between BclI/HindIII, HindIII/XbaI, and BclI/XbaI, respectively. The overall cumulative polymorphism information content (PIC) of these three markers increased from 0.36 to 0.80. Escalation of PIC up to 80% in the present study suggests that haplotyping of factor VIII gene determines better prognosis in the direction of indirect genetic analysis of hemophilia A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation / genetics*
  • DNA Mutational Analysis
  • Factor VIII / genetics*
  • Female
  • Genetic Carrier Screening*
  • Haplotypes*
  • Hemophilia A / blood
  • Hemophilia A / diagnosis*
  • Hemophilia A / genetics
  • Humans
  • India
  • Introns
  • Linkage Disequilibrium*
  • Male
  • Pedigree
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Prognosis
  • Severity of Illness Index

Substances

  • Factor VIII