Carrier detection in Japanese hemophilia A by use of three intragenic and two extragenic factor VIII DNA probes: A study of 24 kindreds

The three factor VIII intragenic restriction fragment length polymorphisms (RFLPs), BcII, XbaI, and BgII, and the two extragenic RFLPs, BgIII/DX13 and TaqI/St14, were analyzed in 60 normal Japanese subjects and 24 families with hemophilia A. The allele frequencies were determined and the extent of linkage disequilibrium among the polymorphisms was assessed. In contrast to intragenic RFLPs of the factor IX gene, intragenic and extragenic RFLPs of the factor VIII gene in Japanese were similar to those observed in whites. As in whites, marked linkage disequilibrium severely compromised the value of the BgII RFLP. The combination of the BcII, XbaI, and TaqI/St14 RFLPs gave 100% carrier detection in the hemophilia A families analyzed.