FACTOR-VIII AND FACTOR-IX GENE POLYMORPHISMS AND CARRIER ANALYSIS IN INDIAN POPULATION

The efficacy of the three common intra- and extragenic polymorphic sit es of the factor VIII and IX genes has been examined in the Indian pop ulation, with an aim to develop a strategy that would be accurate and informative, yet economical, The approach for hemophilia A carrier det ection includes tests for Bcll, Xbal, and Taql polymorphic sites for i ntrons 18 and 22 and the extragenic locus St 14, respectively, whereas for hemophilia B, tests include detection of Taql, Ddel, and Hhal pol ymorphic sites for introns 4 and 1, and the 3' flanking region of the factor IX gene, respectively, In hemophilia A, the cumulative efficien cy of these three polymorphisms has been found to be 100%, since all 3 7 tested families were informative for at least one of these three pol ymorphisms, It is of interest to note that a case of recombination bet ween St 14 and the factor VIII gene was also observed, Of the 47 unrel ated X chromosomes examined (normal = 10, factor VIII:C deficiency = 3 7), heterozygosity for Bcll, Xbal, and St 14 was found to be 47%, 36%, and 86%, respectively, in the factor VIII gene. However, when 37 unre lated X chromosomes (normal = 10, factor IX:C = 27) were analyzed for polymorphism with Taql, Ddel, and Hhal, it was found that the polymorp hism detection rate was only 18% for the Taql site but 45% each for th e Ddel and Hhal sites, in the factor IX gene. This indicates a low eff ectiveness of the Taql restriction site in carrier analysis of hemophi lia B families in our population. (C) 1997 Wiley-Liss, Inc.