Human von Willebrand Factor (vWF): Isolation of Complementary DNA (cDNA) Clones and Chromosomal Localization

Ginsburg, David; Handin, Robert I.; Bonthron, David T.; Donlon, Timothy A.; Bruns, G. A. P.; Latt, Samuel A.; Orkin, Stuart H.

doi:10.1126/science.3874428

Cited by 403 publications

(212 citation statements)

References 33 publications

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“…Methods for growth of yeast and bacteria, as well as procedures for isolation of YAC and BAC DNA, were as previously described (14,15). cDNAs were identified in lambda bacteriophage libraries prepared from human fetal brain (Stratagene) and human umbilical vein endothelial cells (HUVEC) (16) by hybridization of probes to plaque lifts on nylon membranes. Phage DNA was isolated from clones in the HUVEC library according to standard methods (17), and phagemid cDNA clones were rescued from the brain library according to the supplier's instructions.…”

Section: Methodsmentioning

confidence: 99%

Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors

Koontz

Soreng

Nucci

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

353

259

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Endometrial stromal tumors are divided into three types: benign stromal nodules, endometrial stromal sarcomas, and undifferentiated endometrial sarcomas. A variety of cytogenetic abnormalities involving chromosome 7 have been reported in endometrial stromal sarcomas, including a recurrent t(7;17)(p15;q21). We have identified two zinc finger genes, which we have termed JAZF1 and JJAZ1, at the sites of the 7p15 and 17q21 breakpoints. Analyses of tumor RNA indicate that a JAZF1͞JJAZ1 fusion is present in all types of endometrial stromal tumors; however, the fusion appears to be rarer among endometrial stromal sarcomas that would be considered high-grade according to certain classification schemes. These findings suggest that the less malignant endometrial stromal tumors may evolve toward more malignant types, but that some endometrial stromal sarcomas with relatively abundant mitotic activity may compose a biologically distinct group.

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Section: Methodsmentioning

confidence: 99%

Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors

Koontz

Soreng

Nucci

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

353

259

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“…It is possible that there are VWF mutations in these cases outside of the area that we sequenced for this report (i.e. in exons [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]; however, exons 1-17 are not known to be involved with VWF-platelet or collagen interactions, except through the facilitation of multimer assembly. Both cases had RCo/Ag ratios > 0.50, and might be better classified as type 1 VWD cases.…”

Section: Low-vwf:ag Mutation-negative Casesmentioning

confidence: 99%

“…Type 2 VWD is further divided into four subtypes: type 2N is characterized by abnormal binding of VWF to FVIII, type 2A by defective VWF-dependent platelet adhesion because of decreased high molecular weight (HMW) VWF multimers, type 2B by pathologically increased VWF-platelet interactions leading to the depletion of HMW VWF multimers, and type 2M by decreased VWF-platelet interactions not caused by the loss of HMW multimers [4]. The VWF gene was cloned and characterized by four groups simultaneously in 1985 [5][6][7][8], allowing for an improved understanding of the molecular basis of VWD.…”

Section: Introductionmentioning

confidence: 99%

Challenges in defining type 2M von Willebrand disease: results from a Canadian cohort study

Notley

Hegadorn

et al. 2007

Journal of Thrombosis and Haemostasis

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Summary. Background/methods: In order to better characterize the genotype-phenotype correlation in type 2M von Willebrand disease (VWD), we sequenced the coding region for the mature subunit of the von Willebrand factor (VWF) gene (exons 18-52, including exon/intron boundaries) in 16 index cases originally submitted to the Canadian Type 1 VWD Study as type 1 VWD, but reclassified as type 2M VWD on the basis of phenotype (excessive mucocutaneous bleeding and von Willebrand factor: antigen (VWF:Ag) and/or von Willebrand factor: ristocetin cofactor (VWF:RCo) between 0.05 and 0.50 IU mL -1 on at least two occasions and RCo/Ag ratio < 0.6 and no loss of high molecular weight multimers). Available family members (16 affected, 23 unaffected and six unknown) were sequenced for identified mutations. Results: We identified eight different missense mutations (R854Q, T1054M, R1315C, R1374C, R1374H, L1382P, S2179F, and T2647M) within these 16 families. We were significantly more likely to identify a VWF mutation in cases with RCo/Ag ratios < 0.50 (P < 0.05, chisquared test). Importantly, every index case with an RCo/Ag ratio < 0.40 (4/4 index cases) had a mutation identified within the A1 domain, in contrast to 1/12 cases with an RCo/Ag ratio > 0.40. Difficulties with the standardization of the VWF:RCo may be responsible for the heterogeneity in cases with RCo/Ag ratios between 0.40 and 0.60. Conclusions: The genotypephenotype correlation for cases with RCo/Ag ratios < 0.40 is clear. On the basis of our results, the phenotypic definition of type 2M VWD may need to be more stringent, and should be the subject of an international standardization initiative.

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“…Since the cloning of the VWF gene in 1985, [6][7][8][9] significant progress has been made in characterizing the molecular genetic pathology associated with several of the type 2 mutants, and different VWF null alleles have been documented in type 3 VWD. [10][11][12][13][14] In some cases, such as those associated with large VWF gene deletions, treatment with VWF-containing plasma concentrates has been complicated by the development of an anti-VWF antibody response.…”

Section: Introductionmentioning

confidence: 99%

Founder von Willebrand factor haplotype associated with type 1 von Willebrand disease

O’Brien

James

Othman

et al. 2003

Blood

121

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To date, no dominant mutation has been identified in a significant proportion of patients with type 1 von Willebrand disease (VWD). In this study, we examined 70 families as part of the Canadian Type 1 VWD Study. The entire VWF gene was sequenced for 1 index case, revealing 2 sequence variations: intron 30 (5312؊19A>C) and exon 28 at Tyr1584Cys (4751A>G). The Tyr1584Cys variation was identified in 14.3% (10 of 70) of the families and was in phase with the 5312؊19A>C variation in 7 (10.0%) families. Both variants were observed in 2 of 10 UK families with type 1 VWD, but neither variant was found in 200 and 100 healthy, unrelated persons, respectively. Mean von Willebrand factor antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo), and factor VIII coagulant activity (FVIII:C) for the index cases in these families are 0.4 U/mL, 0.36 U/mL, and 0.54 U/mL, respectively, and VWF multimer patterns show no qualitative abnormalities. Aberrant VWF splicing was not observed in these patients, and both alleles of the VWF gene are expressed as RNA. Molecular dynamic simulation was performed on a homology model of the VWF-A2 domain containing the Tyr1584Cys mutation. This showed that no significant structural changes occur as a result of the substitution but that a new solvent-exposed reactive thiol group is apparent. Expression studies revealed that the Tyr1584Cys mutation results in increased intracellular retention of the VWF protein. We demonstrate that all the families with the Tyr1584Cys mutation share a common, evolved VWF haplotype, suggesting that this mutation is ancient. This is the first report of a mutation that segregates in a significant proportion of patients with type 1 VWD. (Blood. 2003;102:549-557)

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Human von Willebrand Factor (vWF): Isolation of Complementary DNA (cDNA) Clones and Chromosomal Localization

Cited by 403 publications

References 33 publications

Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors

Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors

Challenges in defining type 2M von Willebrand disease: results from a Canadian cohort study

Founder von Willebrand factor haplotype associated with type 1 von Willebrand disease

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