BIOLOGIA MOLECOLARE DEL GENE WATSON PDF ->>->>->> https://urllio.com/2sMK3b
Restricting the large PCR fragment to the region of exon 13 coding for the Factor V B-domain revealed 5 polymorphic sites that could be assigned into 2 haplotypes. Sequencing of a 209-bp fragment containing exon 13 and a 6-kb segment corresponding to exon 16 of the FV gene of 7 subjects without the R506Q mutation and of 5 patients with the R506Q mutation revealed the presence of both the F5 C339 and F5 G430 polymorphic sites in all subjects without the R506Q mutation and in 4 of 5 patients with the mutation. The same results were obtained with the G430A mutation of exon 16 of the FV gene. In subjects without the R506Q mutation, these polymorphisms occurred in the normal order, with the exception of an insertion of an adenine residue at positions 3055 in one subject, a characteristic of the R2 allele. In patients with the R506Q mutation, the two polymorphic sites were present in the same order, but inserted at the normal positions, suggesting that R2 encodes a functionally resistant molecule. In 4 patients, the R506Q polymorphism was also present in the 513F/506Q diplotype, which lacks exon 13, and in 2 patients it was present in a 513F/506 Q, 513K/506Q diplotype, a haplotype with a point mutation in the 12th codon of exon 13, which blocks the synthesis of a B domain-deficient molecule. This result suggests that (1) both R2 and R506Q molecules are synthesized in carriers of the 513F/506Q haplotype and (2) R2 and R506Q molecules are synthesized in carriers of the 513F/506Q, 513K/506Q diplotype but only the R506Q is functional.The subtle APC resistance phenotype observed in our study provides evidence for the presence of further FV genetic components that contribute to the APC resistance phenotype and thereby modify the intensity of the protein C anticoagulant pathway. Whether these genetic components were already present in the HR2 haplotype and conferred some resistance properties to FV should be evaluated in future studies using refined phenotypic and functional criteria. Moreover, these genetic components may modulate the intensity of the protein C anticoagulant pathway in vivo, thereby affecting the clinical course of APC resistance.
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