Factor VIII Gene Haplotypes and Linkage Disequilibrium for the Indirect Genetic Analysis of Hemophilia A in India

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.