Factor V gene

Individuals with heterozygous protein C deficiency are seven times more likely to be afflicted with venous thrombosis than normal individuals. A combination of protein C deficiency with a mutation in the factor V gene (factor V Leiden) carries a much greater risk for venous thrombosis than the presence of only one of these conditions (89). 

Dahlback B. Resistance to activated protein C, the Arg506 to Gin mutation in the factor V gene and venous thrombosis. Functional tests and DNA based assays, pros and cons. Thromb Haemost, 1995 73,739-42. 

Parahemophilia is an autosomal recessive bleeding disorder characterized by a reduced plasma concentration of the Factor V blood copulation protein. Deficiency arises from a 12 base-pair deletion in the Factor V gene that impairs the secretion of Factor V by hep-atocytes and results in an abnormal accumulation of immunoreactive Factor V antigen in the cytoplasm. In which region of the Factor V gene would this mutation most likely be located ... 

Chan WR Lee CK, Kwong YL, et al. A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood I 998 91 1 135-1 139. 

Faioni EM, Franchi F, Bucciarelli P, Margaglione M, De Stefano V, Castaman G, et al. Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q. Blood 1999 94 3062-6. 

A mutation in the factor V gene, G to A at 1691, results in the replacement of the normal Arg residue at position 506 in the heavy chain of factor Va by a Gin residue. Individuals carrying this mutation, called factor V (Leiden) are at increased risk of venous thrombosis and venous... 

B. Zoller, B. Dahlback. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet. 1994, 343, 1536-1538. 

In European populations, a point mutation in the Factor V gene (Factor V Leiden) causes the replacement of an arg with a gin in the preferred site for cleavage by activated protein C, rendering Factor Va Leiden resistant to ARC. Heterozygous individuals have a sixfold to eightfold increased risk of deep vein thromboses, and homozygous individuals have a 30- to 140-fold increased risk. The Factor V Leiden mutation does not appear to be associated with increased risk for arterial thrombosis, such as myocardial infarction, except in young women who smoke. 

A mutation in the human Factor V gene plays a major role in causing thrombosis (Factor V Leiden mutation R506Q). The mutation (a G A transversion) that changes the amino acid arginine (codon CGA) to glutamine (cod i CAA) is located at codon 506. The site of this mutation is selected and amplified by PCR in furnishing a DNA of 224 base pairs of which a piece of the antisense sequaice is shown below ... 

Figure 2. MassARRAlF raw spectrum of the MassEXTEM) reaction extending a 23-mer primer with a mixture of dATP, dGTP and ddTTP in a 7 base extension reaction (theoretical mass 9296 Da, found 9297 Da) diagnosing the disease (Mele, i.e. A (Gin) instead ofG (Arg) at the second position of codon 506 of the factor V gene.

Answer B. Decreased Factor V secretion and a corresponding accumulation of cytoplasmic antigen suggest a defect in the translocation of the nascent protein to the endoplasmic reticulum. This implies a mutation in the N-terminal amino acid signal sequence required for targeting to the ER and encoded by the first exon of the gene. 

In addition to its previously mentioned role in copper transport, ceruloplasmin is an amine oxidase, a superoxide dismutase, and a ferrooxidase able to catalyze the oxidation of Fe2+ to Fe3+. Ceruloplasmin contains three consecutive homologous 350-residue sequences which may have originated from an ancestral copper oxidase gene. Like ascorbate oxidase, this blue protein contains copper of the three different types. Blood clotting factors V and VIII (Fig. 12-17), and the iron uptake protein Fet3 (Section A,l) are also closely related. 

Semba, K., Kamata, N., Toyoshima, K., and Yamamoto, T. 1985. A v-erbB-related protooncogene, c-erb-2, is distinct from the c-erbB-l/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc. Natl. Acad. Sci. USA 82 6491-6501. 

Herrmann S-M, Ricard S, Nicaud V et al. Polymorphisms of the tumor necrosis factor-a gene, coronary heart disease and obesity. Eur J Clin Invest. 1998, 28 59-66. 

Arruda, V. R., Schuettrumpf, J., Herzog, R. W. et al. (2004). Safety and efficacy of factor IX gene transfer to skeletal muscle in murine and canine hemophilia B models by adeno-associated viral vector serotype 1. Blood 103(1), 85-92. 

The inherited (primary) hypercoagulable states include activated protein C resistance due to the factor V Leiden mutation, prothrombin gene mutation, antithrombin deficiency, protein C or protein S deficiency, and dysfibrino-genemia. The most important cause of activated Protein C resistance is the defect in factor V involving the mutation of Arg506 to Gln506 (191). 

The Val264Met mutation causes decreased TFPI levels (29). It is reported that the Pro-15 I Leu replacement is a risk factor for venous thrombosis (30). A polymorphism in the 5 UTR of the TFPI gene (-287 T/C did not alter the TFPI levels and did not influence the risk of coronary atherothrombosis (3 I). It has been recently reported that the -33T—>C polymorphism in the intron 7 of the TFPI gene influences the risk of venous thromboembolism, independently of the Factor V Leiden and prothrombin mutations, and its effect is mediated by increased total TFPI levels (32). 

Ameziane N, Seguin C, Borgel D, et al, The -33T— C polymorphism in intron 7 of the TFPI gene influences the risk of venous thromboembolism, Independently of Factor V Leiden and Prothrombin mutations, Thromb Haemost 2002 88 195-1 99,... 

Ekstrand, A. J., Sugawa, N., James, C. D., and Collins, V. P. (1992). Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc. Natl. Acad. Sci. U.S.A. 89, 4309—4313. 

Oram 93 5x 106 Natural immunized (factor VII) PCR fd, PCR VL, V genes Mouse spleen Fab Phagemid 10 1 10-9... 

---