Microsatellite Polymorphisms in Intron 13 and Intron 22 of Factor VIII Gene

Cho, Sang Hee; Cho, Youl Hee; Shim, Sung Han; Seo, Han Kyu; Hwang, Yoon Young; Moon, Hyung; Lee, Jai Auk; Chung, Sung Ro

Abstract

The factor VIII gene comprises 26 exons spanning 185kb of DNA located at the distal end of the long arm of the X-chromosome, Defects in this gene cause hemophilia A, a bleeding disorder affecting 1/10,000 males. Linkage analysis is known as an efective method for the prenatal diagnosis and for the identification of carrier status. Several polymorphic markers had been studied to establish the diagnostic procedure for hemophilia A in Korea, and heterozygosity of 96% could be expected with 4 markers such as St14.1/Taq I, intron 18/Bcl I, intron 22/Xba I and DX13/Bal II. But in some families, above markers were not informative, and it was required another polymorphic markers should be applied for the diagnosis. Two recently identified microsatellite polymorphisms in intron 13 and intron 22 of FVIII gene were investigated to increase the heterozygosity and to diagnose previously uninformative families. Intron 13(CA)n repeats polymorphism showed 7 alleles with expected heterozygosity of 0.5336. Intron 22(CA)n(TC)n repeats polymorphism showed 4 alleles with expected heterozygosity of 0.5146. With the two microsatellite polymorphisms we could expect the heterozygosity of 0.6756. And we could successfully perform prenatal diagnosis previously uninformative family with intron 13 microsatellite polymorphism. With 4 polymorphisms detected by polymerase chain rection(intron 13 and intron 22 microsatellite polymorphisms, intron 18/Bcl I and St14.1 VNTR/Taq I), about 97% of hemophilia A family in Korea would be diagnosed by linkage analysis.