Summary
We have used the polymerase chain reaction to amplify two variable number of tandem repeats (VNTRs) within a region of repetitive DNA located in intron 40 of the von Willebrand factor (vWf) gene. Heterozygosity for VNTR I was observed in 30 out of 39 normal unrelated individuals tested (77%), and for VNTR II in 29 out of 44 (66%) similar individuals. Family studies were carried out on 11 kindreds with von Willebrand disease (vWD). Ten of these families were found to be informative for one or other of the VNTRs or for a combination of data from both VNTRs. This method can be used for antenatal diagnosis and for carrier diagnosis in recessive forms of vWD. It is also useful for tracking the gene associated with vWD in type I families where there may be one or more individuals with a phenotypically uncertain diagnosis.
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References
Ball J, Warnock LJ, Preston FE (1990) Rapid assessment of haemophilia A carrier state by non-invasive techniques using the polymerase chain reaction. J Clin Pathol 43:505–507
Bernardi F, Guerra S, Patracchini P, Volinia S, Buzzoni D, Ballerini G, Casonato A, Marchetti G (1988) Von Willebrand's disease investigated by two novel RFLPs. Br J Haematol 68:243–248
Bignell P, Standen GR, Bowen DJ, Peake IR, Bloom AL (1990) Rapid neonatal diagnosis of von Willebrand's disease by use of the polymerase chain reaction. Lancet 336:638–639
Ginsburg D, Handin RI, Bonthron DT, Donion TA, Bruns GAP, Latt SA, Orkin SH (1985) Human von Willebrand factor (vWf): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science 228:1401–1406
Hardisty RM, MacPherson JC (1962) A one-stage factor VIII (anti-haemophilic globulin) assay and its use on venous and capillary plasma. Thrombos Diathes Haemorrh 7:215–229
Ivy AC, Nelson D, Bucher D (1940) The standardisation of certain factors in the cutaneous venostasis bleeding time technique. J Lab Clin Med 26:1812–1822
Kogan S, Gitschier J (1990) Genetic prediction of haemophilia A. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds) PCR protocols: a guide to methods and applications. Academic Press, San Diego, pp 288–299
Lych DC, Zimmerman TS, Collins CJ, Brown M, Morin MJ, Ling EH, Livingstone DM (1985) Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell 41:49–56
MacFarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson J (1975) A method for assaying von Willebrand factor (ristocetin cofactor). Thrombos Diathes Haemorrh 34:306–308
Mancuso DJ, Tuley EA, Westfield LA, Worrall NK, Shelton-Inloes BB, Sorace JM, Alevy YG, Sadler JE (1989) Structure of the gene for human von Willebrand factor. J Biol Chem 264:19514–19527
Nagamine CM, Chan K, Lau YC (1989) A PCR artefact: generation of heteroduplexes. Am J Hum Genet 45:337–339
Peake IR, Liddell MB, Moodie P, Standen G, Mancuso DJ, Tuley EA, Westfield LA, Sarace JM, Sadler JE, Verweij CL, Bloom AL (1990a) Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual. Blood 75:654–661
Peake IR, Bowen D, Bignell P, Liddell MB, Sadler JE, Standen G, Bloom AL (1990b) Family studies and prenatal diagnosis in severe von Willebrand's disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene. Blood 76:555–561
van Ploos Amstel HK, Reitsma PH (1990) Tetranucleotide repeat polymorphism in the vWf gene. Nucleic Acids Res 18:4957
Rodeghiero F, Castaman G, Dini E (1987) Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 69:454–459
Ruggeri ZM, Zimmerman TS (1981) The complex multimeric composition of factor VIII/von Willebrand factor. Blood 57:1140–1143
Ruggeri ZM, Zimmerman TS (1987) Von Willebrand factor and von Willebrand disease. Blood 70:895–904
Sadler JE, Shelton-Inloes BB, Sorace JM, Harlan JM, Titani K, Davie EW (1985) Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci USA 82:6394–6398
Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Hinuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
Shelton-Inloes BB, Chehab FF, Mannucci PM, Federici AB, Sadler JE (1987) Gene deletions correlate with the development of alloantibodies in von Willebrand disease. J Clin Invest 79:1459–1465
Standen GR, Bignell P, Bowen DJ, Peake IR, Bloom AL (1990) Family studies in von Willebrand's disease by analysis of restriction fragment length polymorphisms and an intragenic variable number tandem repeat (VNTR) sequence. Br J Haematol 76:242–249
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Cumming, A.M., Armstrong, J.G., Pendry, K. et al. Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease. Hum Genet 89, 194–198 (1992). https://doi.org/10.1007/BF00217122
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DOI: https://doi.org/10.1007/BF00217122