Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A

Lakich, D.; Kazazian, H. H., Jr.; Antonarakis, Stylianos; Gitschier, J.

doi:10.1038/ng1193-236

Scientific article

English

Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A

Contributors

Lakich, D.; Kazazian, H. H., Jr.; Antonarakis, Stylianos; Gitschier, J.

Published in

Nature genetics, vol. 5, no. 3, p. 236-241

Publication date

1993

Abstract

Mutations in the factor VIII gene have been discovered for barely more than half of the examined cases of severe haemophilia A. To account for the unidentified mutations, we propose a model based on the possibility of recombination between homologous sequences located in intron 22 and upstream of the factor VIII gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. We present evidence to support this model and describe a Southern blot assay that detects the inversion. These findings should be valuable for genetic prediction of haemophilia A in approximately 45% of families with severe disease.

Keywords

Base Sequence
Blotting, Southern
Cell Line, Transformed
Chromosome Inversion
DNA Primers
Exons
Factor VIII/ genetics
Hemophilia A/ genetics
Humans
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
Recombination, Genetic

UNIGE affiliation entities

Faculté de médecine / Section de médecine clinique / Département de médecine

Citation (ISO format)

LAKICH, D. et al. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. In: Nature genetics, 1993, vol. 5, n° 3, p. 236–241. doi: 10.1038/ng1193-236

Article

Identifiers

PID : unige:8840
DOI : 10.1038/ng1193-236
PMID : 8275087

Additional URL for this publication

http://www.nature.com/ng/journal/v5/n3/pdf/ng1193-236.pdf

Journal ISSN

1061-4036

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Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

Citation (ISO format)

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Additional URL for this publication

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation