Evidence that platelet and plasma fibrinogen have the same A-alpha chain gene product

1986 ◽  
pp. 15-22
Author(s):  
Christopher Southan ◽  
Irina Knight ◽  
Helen Ireland ◽  
David A. Lane
Keyword(s):  
Gene Product ◽  
Plasma Fibrinogen ◽  
Chain Gene ◽  
Alpha Chain

scholarly journals Fibrinogen Marburg: a homozygous case of dysfibrinogenemia, lacking amino acids A alpha 461-610 (Lys 461 AAA-->stop TAA)

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1972-1979 ◽  
Author(s):  
J Koopman ◽  
F Haverkate ◽  
J Grimbergen ◽  
R Egbring ◽  
ST Lord
Keyword(s):  
Disulfide Bonds ◽  
Stop Codon ◽  
Polyclonal Antibodies ◽  
Functional Method ◽  
Terminal Segment ◽  
Plasma Fibrinogen ◽  
Base Substitution ◽  
Chain Gene ◽  
Fibrinogen Concentration ◽  
Alpha Chain

In the A alpha-chain gene coding for an abnormal fibrinogen (fibrinogen Marburg) we identified a single base substitution (A-->T) that changes the codon A alpha 461 AAA (Lys) to TAA (Stop). The propositus was found to be homozygous for the mutation, whereas the father and five siblings were heterozygous, and three other siblings contained only the normal sequence. The stop codon at position 461 results in the deletion of the carboxyl-terminal segment A alpha 461–610. Purified fibrinogen Marburg contained an A alpha-chain with a relative molecular weight of approximately 47,000. The FpA release by thrombin was not affected by this deletion, whereas the fibrin polymerization was strongly decreased. The binding of endothelial cells to immobilized fibrinogen Marburg was almost completely abolished compared with normal fibrinogen. Fibrinogen Marburg contained a substantial amount of albumin linked to the fibrinogen molecule by disulfide bonds, and these fibrinogen-albumin complexes were also present in plasma. The plasma fibrinogen concentration of the propositus was measured by three different methods: a functional method (< 0.25 mg/mL), an immunologic method using polyclonal antibodies (0.6 mg/mL), and an immunologic method based on two monoclonal antibodies specific for the amino- terminus and carboxyl-terminus of the A alpha-chain (< 0.05 mg/mL). Using the two immunologic methods, it appeared that only 10% to 15% of the plasma fibrinogen of the heterozygous siblings was abnormal.

scholarly journals A frame shift mutation in the fibrinogen A alpha chain gene in a kindred with renal amyloidosis

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4197-4203 ◽  
Author(s):  
T Uemichi ◽  
JJ Liepnieks ◽  
T Yamada ◽  
MA Gertz ◽  
N Bang ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Mutant Gene ◽  
Single Strand Conformation Polymorphism ◽  
Plasma Fibrinogen ◽  
Chain Gene ◽  
Renal Amyloidosis ◽  
Polymorphism Analysis ◽  
Alpha Chain ◽  
Frame Shift ◽  
Frame Shift Mutation

A new American kindred with amyloidosis was found by single-strand conformation polymorphism analysis to have a mutation in the fibrinogen A alpha chain gene. Affected members in this kindred have autosomal dominant amyloid nephropathy. DNA sequencing showed a single nucleotide deletion at the third base of codon 524 of the fibrinogen A alpha chain genes (4904delG) that resulted in a frame shift and premature termination of the protein at codon 548. Antiserum was produced to a portion of the abnormal peptide predicted by the DNA sequence and amyloid deposits were immuno-histologically proven to contain this abnormal peptide. Two of the propositus' 4 children were positive for the mutant fibrinogen A alpha chain gene by restriction fragment length polymorphism analysis based on polymerase chain reaction. These two mutant gene carriers now in the second decade of life show no clinical symptoms of amyloidosis as yet but have lower plasma fibrinogen concentrations when compared with their normal siblings. This the first description of a kindred with renal amyloidosis and low plasma fibrinogen and also the first report of amyloidosis caused by a frame shift mutation.

scholarly journals Fibrinogen Marburg: a homozygous case of dysfibrinogenemia, lacking amino acids A alpha 461-610 (Lys 461 AAA-->stop TAA)

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1972-1979 ◽  
Author(s):  
J Koopman ◽  
F Haverkate ◽  
J Grimbergen ◽  
R Egbring ◽  
ST Lord
Keyword(s):  
Disulfide Bonds ◽  
Stop Codon ◽  
Polyclonal Antibodies ◽  
Functional Method ◽  
Terminal Segment ◽  
Plasma Fibrinogen ◽  
Base Substitution ◽  
Chain Gene ◽  
Fibrinogen Concentration ◽  
Alpha Chain

Abstract In the A alpha-chain gene coding for an abnormal fibrinogen (fibrinogen Marburg) we identified a single base substitution (A-->T) that changes the codon A alpha 461 AAA (Lys) to TAA (Stop). The propositus was found to be homozygous for the mutation, whereas the father and five siblings were heterozygous, and three other siblings contained only the normal sequence. The stop codon at position 461 results in the deletion of the carboxyl-terminal segment A alpha 461–610. Purified fibrinogen Marburg contained an A alpha-chain with a relative molecular weight of approximately 47,000. The FpA release by thrombin was not affected by this deletion, whereas the fibrin polymerization was strongly decreased. The binding of endothelial cells to immobilized fibrinogen Marburg was almost completely abolished compared with normal fibrinogen. Fibrinogen Marburg contained a substantial amount of albumin linked to the fibrinogen molecule by disulfide bonds, and these fibrinogen-albumin complexes were also present in plasma. The plasma fibrinogen concentration of the propositus was measured by three different methods: a functional method (< 0.25 mg/mL), an immunologic method using polyclonal antibodies (0.6 mg/mL), and an immunologic method based on two monoclonal antibodies specific for the amino- terminus and carboxyl-terminus of the A alpha-chain (< 0.05 mg/mL). Using the two immunologic methods, it appeared that only 10% to 15% of the plasma fibrinogen of the heterozygous siblings was abnormal.

Sequence variants in the FcεRI alpha chain gene

2002 ◽  
Vol 93 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Toshiki Shikanai ◽  
Eric S. Silverman ◽  
Brian W. Morse ◽  
Craig M. Lilly ◽  
Hiroshi Inoue ◽  
...  
Keyword(s):  
Promoter Region ◽  
Population Substructure ◽  
Chain Gene ◽  
Polymorphism Analysis ◽  
Sequence Variants ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Alpha Chain ◽  
Asthmatic Patients ◽  
Single Stranded Conformational Polymorphism

There is a relationship between IgE levels and expression of high-affinity IgE receptors (FcεRI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the FcεRI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the FcεRI alpha chain gene with genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by using single-stranded conformational polymorphism analysis. No nonsynonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A/C transversion at −770 from the translation start site; a G/A transition at −664; and a T/C transition at −335. No differences in allele frequencies were detected between asthmatic subjects and controls. Homozygosity for the C variant at locus −335 was more common in Caucasian asthmatic patients with IgE levels in the lower quartile than in the upper quartile ( P = 0.032). An analysis of highly polymorphic SNPs indicated that this association is unlikely to be due to population substructure. We conclude that homozygosity for the C allele of FcεRI alpha chain variant is associated with lower IgE levels.

scholarly journals A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III

1994 ◽  
Vol 269 (52) ◽  
pp. 33129-33134
Author(s):  
M Furlan ◽  
C Steinmann ◽  
M Jungo ◽  
C Bögli ◽  
F Baudo ◽  
...  
Keyword(s):  
Frameshift Mutation ◽  
Chain Gene ◽  
Alpha Chain

scholarly journals Common structural genes for platelet and plasma fibrinogen

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 120-126 ◽  
Author(s):  
B Teige ◽  
G Gogstad ◽  
F Brosstad ◽  
B Olaisen
Keyword(s):  
Plasma Fibrinogen ◽  
Two Dimensional ◽  
Structural Genes ◽  
Gamma Chain ◽  
Two Dimensional Electrophoresis ◽  
Alpha Chain ◽  
Variant Pattern ◽  
Different Sources ◽  
Dimensional Electrophoresis

Abstract Fibrinogen from plasma was compared with fibrinogen from platelets using two-dimensional electrophoresis. The source of platelet fibrinogen was isolated alpha-granules, thrombin- and collagen-released platelet material. The B beta- and gamma-chains from the different sources showed similar two-dimensional patterns, while gamma'-chains were not observed in platelet fibrinogen preparations. Furthermore, the A alpha-chain could hardly be identified in platelet preparations. When individual fibrinogen was studied in persons heterozygous for genetic B beta- and gamma-chain variants, the two-dimensional variant pattern could be demonstrated in plasma fibrinogen as well as in platelet fibrinogen. This observation strongly indicates that the structural genes for plasma and platelet fibrinogen B beta- and gamma-chains are identical.

scholarly journals A delta T-cell receptor deleting element transgenic reporter construct is rearranged in alpha beta but not gamma delta T-cell lineages.

1995 ◽  
Vol 15 (12) ◽  
pp. 7022-7031 ◽  
Author(s):  
J Shutter ◽  
J A Cain ◽  
S Ledbetter ◽  
M D Rogers ◽  
R D Hockett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gamma Delta ◽  
Alpha Chain ◽  
Chain Locus ◽  
Discrete Population ◽  
Alpha Beta ◽  
Gamma Delta T Cell

T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell.

scholarly journals Human platelet fibrinogen gamma chain structure

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 990-995 ◽  
Author(s):  
MW Mosesson ◽  
GA Homandberg ◽  
DL Amrani
Keyword(s):  
Protein A ◽  
Structural Difference ◽  
Electrophoretic Analysis ◽  
Chain Structure ◽  
Plasma Fibrinogen ◽  
Factor Xiiia ◽  
Single Type ◽  
Chain Gene ◽  
Gamma Chain ◽  
Parenchymal Cells

Abstract Human plasma fibrinogen is produced by liver parenchymal cells. Such molecules contain two classes of gamma-chains (gamma A, gamma'), which differ with respect to their COOH-terminal sequences. When fibrin is crosslinked in the presence of factor XIIIa and Ca2+, three types of gamma-dimer are formed (gamma A-gamma A; gamma A-gamma'; gamma'- gamma'). A separate fibrinogen pool is located in platelet alpha- granules. We analyzed this fibrinogen to determine whether gamma'- chains were present to the same extent (7%) that they are found in plasma fibrinogen. Electrophoretic analysis (Laemmli system) of reduced samples of the clot that formed subsequent to release of fibrinogen from thrombin-stimulated washed platelets, revealed a single crosslinked gamma-dimer band in the gamma A-gamma A position. Material collected into EDTA-containing buffer and subsequently crosslinked in the presence of added factor XIII and Ca2+ also revealed a gamma A- gamma A dimer band. This finding was further investigated by Western blotting of reduced gel specimens that had been reacted with an anti- gamma-chain antibody followed by 125I-labeled protein A. A single type of gamma-chain, gamma A, was present in the fibrinogen from a Triton X- 100 or 10 M urea platelet lysate, or in noncrosslinked fibrin obtained from thrombin-treated platelets. Crosslinked reduced fibrin from thrombin-treated platelets or that prepared from the Triton lysate revealed a single type of gamma-dimer, gamma A-gamma A. We conclude that there are no gamma'-chains (less than 1%) in platelet fibrinogen. This structural difference from hepatic fibrinogen probably results from differences in the processing and/or regulation of the fibrinogen gamma-chain gene in megakaryocytes.

scholarly journals Polymorphism rs2066865 in the Fibrinogen Gamma Chain (FGG) Gene Increases Plasma Fibrinogen Concentration and Is Associated with an Increased Microvascular Thrombosis Rate

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 563 ◽  
Author(s):  
Karina Drizlionoka ◽  
Jānis Zariņš ◽  
Agnese Ozoliņa ◽  
Liene Ņikitina-Zaķe ◽  
Biruta Mamaja
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Plasma Fibrinogen ◽  
Secondary Outcome ◽  
Chain Gene ◽  
Fibrinogen Concentration ◽  
Nucleotide Polymorphism ◽  
Flap Surgery ◽  
Gamma Chain ◽  
Single Nucleotide ◽  
Microvascular Flap

Background and Objective: Thrombosis due to inherited hypercoagulability is an issue that has been raised in microvascular flap surgery previously. We analyzed the association of a single nucleotide polymorphism (SNP) in rs2066865 in the fibrinogen gamma chain (FGG) gene, alteration in plasma fibrinogen concentration, and presence of microvascular flap thrombosis. Materials and Methods: A total of 104 adult patients with microvascular flap surgery were subjected to an analysis of the presence of SNP rs2066865 in the FGG gene. Alterations in plasma fibrinogen concentration according to genotype were determined as a primary outcome, and flap thrombosis was defined as a secondary outcome. Results: Flap thrombosis was detected in 11.5% of patients (n = 12). Successful revision of anastomosis was performed in four patients, resulting in a microvascular flap survival rate of 92.3%. We observed an increase in plasma fibrinogen concentration in genotype G/A and A/A carriers (G/G, 3.9 (IQR 4.76-3.04); G/A, 4.28 (IQR 5.38-3.18); A/A, 6.87 (IQR 8.25-5.49) (A/A vs. G/A, p = 0.003 and A/A vs. G/G, p = 0.001). Within group differences in microvascular flap thrombosis incidence rates were observed—G/G 6/79 (7.59%); G/A 5/22 (22.7%); A/A 1/3 (33.3%) (OR 0.30 95%; CI 0.044 to 0.57), p = 0.016; RR 3.2—when G/G versus G/A and A/A were analyzed respectively. Conclusions: A/A and G/A genotype carriers of a single nucleotide polymorphism in rs2066865 in the fibrinogen gamma chain gene had a higher plasma fibrinogen concentration, and this might be associated with an increased microvascular flap thrombosis incidence rate. Determined polymorphism could be considered as a genetic marker associated with microvascular flap thrombosis development. To confirm the results of this study, the data should be replicated in a greater sample size.

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