Human plasma fibrinogen heterogeneity: evidence for an extended carboxyl-terminal sequence in a normal gamma chain variant (gamma').

Abstract

Two types of normal human plasma fibrinogen-peak 1 and peak 2-are distinguishable by DEAE-cellulose gradient elution chromatography. The elution characteristics of peak 2 fibrinogen, which amounts to about 15% of the total, are attributable to the presence of a 'y chain variant, 7y', which is more negatively charged than 7y chains and makes up (DNScad) showed that the same amount of this compound could be incorporated covalently into either type of 7 chain. Furthermore, the DNScad-labeled COOH-terminal CNBr fragment (CNBr e) derived from the S-carboxymethylated -y chain was smaller than

Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen γ′ levels

“…10 Nearly all the ␥Ј protein occurs in vivo as a heterodimer with the ␥A variant in which one D region contains a ␥Ј carboxyl terminus and the other a ␥A carboxyl terminus (␥A/␥Ј fibrinogen). 23 For personal use only. on May 11, 2018.…”

“…19 Five haplotypes in the FGG gene, 7 in the FGA gene, and 7 in the FGB gene were found. 8,20 To tag these haplotypes, we identified 15 htSNPs ( Figure 1A) [21][22][23] Genotyping of FGB was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. Genotyping of FGA and FGG was performed using the 5Ј nuclease/TaqMan assay.…”

Genetic analyses of novel compound heterozygous hypodysfibrinogenemia, Tsukuba I: FGG c.1129+62_65 del AATA and FGG c.1299+4 del A

“…The major A-chain (98-99% of the A-chain) contains 610 residues (translated from the first five exons of FGA), while the alternative A-chain (1-2% of the A-chain) contains 846 residues and is translated from all six exons of FGA [4]. The predominant form of the -chain, A (85-93% of the -chain) contains 411 residues, and the variant form of the -chain, ' (7-15% of the -chain) consists of 427 residues [5,6]. The A-chain is produced by the translation of all 10 FGG exons, while the '-chain is produced by alternative splicing and polyadenylation of the -chain mRNA transcript, resulting in the translation of exons 1-9 of FGG [7,8].…”

“…The A-chain is produced by the translation of all 10 FGG exons, while the '-chain is produced by alternative splicing and polyadenylation of the -chain mRNA transcript, resulting in the translation of exons 1-9 of FGG [7,8]. A major fraction (84%) of plasma fibrinogen contains a homodimer referred to as (A-B-A)2orA/A,and the minor fraction contains a heterodimer (15% of plasma fibrinogen) referred to as (A-B-A(A-B-') orA/' and a homodimer (1% of plasma fibrinogen) referred to as (A-B-')2 or '/' [5,6]. 5 More than 300 different mutations in the fibrinogen genes, FGA, FGB, and FGG, have been associated with the phenotype of afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, renal amyloidosis, or fibrinogen storage disease, as listed in the fibrinogen variant data base [9].…”

“…As a consequence, we detected a high-molecular-weight aberrant '-chain in the Western blot analysis of fibrinogen from the plasma of our patient. Although the mechanism underlying alternative splicing for '-chain mRNA production [7,8] and the regulation of plasma '-chain levels have not yet been elucidated in detail, plasma fibrinogen contains approximately 7 to 15% '-chains and exists as three types of molecules: AA (84% of total plasma fibrinogen), A' (15%), and '' (1%) [5,6]. The normal '-chain is synthesized at markedly smaller amounts than the normal A-chain.…”