1Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
Thirteen individuals (13%) were hemizygous for sequence variations in the coding region of
A significant proportion of control individuals carried sequence variations in
Hemophilia A and B are X-linked recessive bleeding disorders deficient coagulation factor VIII (FVIII) and IX (FIX), respectively. Mutations in
The DNA samples were obtained from 100 male control individuals of Korean descent (total, 100 X chromosomes). They had normal prothrombin time (PT), aPTT, FVIII activity (%), and liver function tests. Since FVIII is an acute-phase reactant, we confirmed that the study subjects had a normal level of C-reactive protein. Genomic DNA was isolated from the peripheral blood leukocytes of study subjects using the Wizard Genomic DNA Purification Kit, according to the manufacturer's instructions (Promega, Madison, WI, USA). All exons and their flanking intronic sequences of
The frequency of coding sequence variations were described using the observed frequency and standard error. The comparison of FVIII activities between 2 groups with and without a variation of interest was performed by Mann-Whitney test. A P value less than 0.05 was considered statistically significant. All statistical analyses were performed using MedCalc statistical software, Version 11.5.1 (MedCalc Software, Mariakerke, Belgium).
Thirteen individuals (13%) were shown to be hemizygous for a sequence variation in the coding sequence of
Historically, linkage analysis was used to determine the mutation status in individuals with hemophilia [9-11]. In recent years, direct mutation detection techniques such as direct sequencing analysis, targeted mutation analysis (intron 22 and intron 1 inversion mutations of
In the present study, we obtained a set of variation data for the
The results obtained in this study can be used as a reference dataset for molecular diagnosis of hemophilia A and B in Korea. In addition, the data we obtained revealed rare SNPs, including one enlisted as a missense mutation causing hemophilia A. The data presented here indicate that interpretation of sequencing data using public databases to diagnose hemophilia A and B should be approached cautiously. It should also be noted that the number of chromosomes (100) used in this study has a limitation in identifying other rare SNPs, especially those with a minor allele frequency <1% .
The distribution of factor VIII activity levels of the carriers and non-carriers of 2 common polymorphisms Asp1260Glu
Alignment of the