Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence

Journal Article · Tue Mar 15 04:00:00 EST 1994 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.91.6.2221· OSTI ID:86518

Eikenboom, J C; Brieet, E; Reitsma, P H; Vink, T; Sixma, J J ^[1]

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1. Univ. Hospital, Utrecht (Netherlands)

The authors have analyzed a type IIB and a type I von Willebrand disease family for the presence of mutations in the region coding for the glycoprotein Ib binding domain of the von Willebrand factor. Since this sequence is also present in the highly homologous von Willebrand factor pseudogene, the authors have studied genomic DNA as well as cDNA, which was produced from RNA isolated from endothelial cells or platelets. In both families, they have detected multiple consecutive nucleotide substitutions in the 5{prime} end of exon 28 that result in a sequence identical to the von Willebrand factor pseudogene. These substitutions were also found in cDNA, which proves that they are present in the active gene. The occurrence of multiple adjacent substitutions that exactly reflect a part of the sequence of the von Willebrand factor pseudogene is difficult to reconcile with sequential single mutational events. They therefore hypothesize that each of these multiple substitutions arose from one recombinational event between gene and pseudogene. 34 refs., 4 figs., 2 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 86518
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 6 Vol. 91; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BLOOD COAGULATION FACTORS
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
HEREDITARY DISEASES
HUMAN CHROMOSOME 22