Evaluation of Hemophilia A Families to Detect Carriers Using Gene Linkage in Mazandaran Province

Hemophilia A is an X-linked recessive inherited disease that its frequency is reported as 1 in 5000 to 10000 males. Linkage analysis is widely used in related female of hemophilic family around the world. In this study, 3 intragenic polymorphism markers including G/A in intron 7, T/A polymorphism in intron 18 and C/T polymorphism in intron 19 were introduced as the most informative markers for the linkage analysis of factor eight gene. This research was designed to determine the carrier people and give knowledge to the families in risk for the birth of another affected child on those families. In this cross-sectional study, 20 hemophiliacs A families including 30 patients and 64 family members (father, mother, sisters, aunt, and their children and other relative, who had chance to be carrier) from 5 cities of Mazandaran province were investigated. At first, family history was collected and pedigree was drawn. Five to 10 milliliter peripheral bloods were collected from each person and then DNA was extracted. Molecular study was performed using ARMS-PCR method and using three mentioned markers. At last, carrier persons were identified regarding to the inheritance of the same affected chromosome in patients and other related females in the family and comparison of linkage phase in affected person and results achieved from related females. From 95 individuals who were studied in 20 families, 28 related women to the hemophilia patients were diagnosed as obligate or possible carriers. Also the usefulness of each markers applied in this study were evaluated by calculation of the coefficient of heterozygocity for each polymorphic makers and following results were achieved: G/A in intron 7 (49.4%), T/A in intron 18 (41.17%) and C/T in intron 19 (42.35%). The results showed that polymorphic markers used in this study were highly informative and suitable for carrier detection of hemophilia A.