Screening of intron 1 inversion and three intragenic factor VIII gene polymorphisms in Pakistani hemophilia A families
| Autor: | Rubina Hafeez, Shahla Sohail, Warda Fatima, Saima Mansoor Bugvi, Saqib Mahmood, Muhammad Imran |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Linkage disequilibrium Genetic Linkage Population Biology HindIII Hemophilia A Genetic linkage hemic and lymphatic diseases Humans Mass Screening Genetic Predisposition to Disease Pakistan Allele Child education Alleles Genetics education.field_of_study Factor VIII Polymorphism Genetic Intron Hematology General Medicine Introns Genetic marker Chromosome Inversion biology.protein Female Restriction fragment length polymorphism |
| Zdroj: | Blood Coagulation & Fibrinolysis. 23:132-137 |
| ISSN: | 0957-5235 |
| DOI: | 10.1097/mbc.0b013e32834eb95a |
| Popis: | Indirect linkage analysis using highly informative polymorphic markers is the method of choice for carrier detection of hemophilia A in developing countries because direct DNA or mRNA sequence analysis is manifold costly and difficult than indirect gene tracking. Worldwide populations have revealed marked variation in the informativeness of polymorphic markers because of which each country has to select its own panel of markers for linkage analysis in hemophilia A families. The present study aimed at determining the informativeness of three factor VIII gene polymorphisms [intron 13(CA)n repeats, HindIII and AlwNI] in the Pakistani population. One hundred and forty-three individuals from 32 hemophilia A families and 68 unrelated anonymous females from the general population were screened for these polymorphisms using PCR and RFLP techniques. An inversion in intron 1 of the factor VIII gene causing 2-5% of severe hemophilia A cases was also screened in 128 Pakistani hemophilia A patients. None of the affected individuals carried the intron 1 inversion at least in peripheral blood leucocytes. The informativeness of intron 13 repeats, HindIII and AlwNI was 59.1% (13/22 hemophilia A families revealing five different alleles), 40.6% (13/32 hemophilia A families) and 6.25% (2/32 hemophilia A families), respectively. The cumulative informativeness of intron 13 repeats and HindIII was 63.6% (14/22 hemophilia A families), revealing strong linkage disequilibrium between these two polymorphic markers. These results suggest that there is a need to determine the informativeness of other polymorphic markers of the factor VIII gene to achieve 100% success rate for carrier detection of hemophilia A in Pakistan. |
| Databáze: | OpenAIRE |
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