title: 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.
authors.affiliation: Molecular Genetics Laboratory, Department of Human Biology, Punjabi University, Patiala, India. singh_m12@rediffmail.com
authors.forename: Monica
authors.initials: M
authors.lastname: Singh
authors.forename: Puneetpal
authors.initials: P
authors.lastname: Singh
mesh_terms: D001777:Blood Coagulation / Q000235:genetics*; D004252:DNA Mutational Analysis; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007194:India; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D005169:Factor VIII