StatusThe thesis was presented on the 20 May, 2010
Approved by NCAA on the 5 July, 2010
Abstract– 1.90 Mb / in russian
– 1.84 Mb / in romanian
The thesis consists of introduction, 4 chapters, conclusions and recommendations, 159 bibliographic sources, 5 annexes, 96 pages, 12 tables and 29 pictures. The obtained results have been published in 11 scientific papers.
Key words: hemophilia, F8 and F9 genes, coagulation factors VIII and IX, genotype, mutations, polymorphic loci, molecular diagnosis.
Research field: 03.00.15 – Genetics
Research goal: molecular analysis of the F8 and F9 genes in families with hemophilia A and B.
Aims: to create a DNA bank of families with hemophilia A and B, to analyze coding regions and exon-intron junctions of the F8 and F9 genes in patients with hemophilia A and B, to study polymorphic loci of the genes and to identify allelic associations between loci within genes, to develop molecular diagnostics laboratory system for prophylaxis of hemophilia A and B in Moldova.
Scientific innovation. For the first time in Moldovan patients with hemophilia A and B the spectrum of mutations in the F8 and F9 genes and their frequency were determined, 17 novel mutations were identified. Data regarding allele desstributtion and linkage disequilibrium of polymorphic loci within these genes was obtained.
Theoretical significance. New data that enlage molecular insights of hemophilia was gained. Novel missense mutations were characterized based on current knowledge of factor VIII crystal structure.
Practical importance. There was created a DNA bank of patients with hemophilia and their family members (198 samples). Mutations in the F8 and F9 genes were identified. The elaborated molecular diagnostics system permits to detect up to 85,7% mutations in the F8 gene and 100% — in F9 gene. The obtained results allow the identification of at-risk alloimmune inhibitor patients with hemophilia A, female carries and were used in prenatal diagnosis.
The obtained results are implemented for hemophilia genetic counseling at the National Center of Reproductive Health and Medical Genetics.