Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees

Weikuan Gu, Marjory Brooks, James Catalfamo, Jharna Ray, Kunal Ray

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The molecular defects causing severe factor IX deficiency were identified in two distinct canine breed-variants. Both defects were associated with an absence of plasma factor IX coagulant activity and antigen. A large deletion mutation was found in 1 breed variant, spanning the entire 5' region of the factor IX gene extending to exon 6. An approximately 5 kb insertion disrupted exon 8 of the second breed-variant. This insertion was associated with alternative splicing between a donor site 5' and acceptor site 3' to the normal exon 8 splice junction, with introduction of a new stop codon. The resultant transcript lacked most of the factor IX catalytic domain and 3' untranslated region. Molecular analyses of canine hemophilia B define an experimental model for study of inhibitor formation and gene therapy strategies, and provide insight into spontaneous mutation mechanisms in the factor IX gene and on the X chromosome of mammalian species.

Original languageEnglish (US)
Pages (from-to)1270-1275
Number of pages6
JournalThrombosis and Haemostasis
Volume82
Issue number4
StatePublished - Oct 20 1999
Externally publishedYes

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Hemophilia B
Factor IX
Pedigree
Canidae
Exons
Mutation
Coagulants
X-Linked Genes
Terminator Codon
Sequence Deletion
Alternative Splicing
3' Untranslated Regions
Genetic Therapy
Catalytic Domain
Theoretical Models
Antigens
Genes

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Gu, W., Brooks, M., Catalfamo, J., Ray, J., & Ray, K. (1999). Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees. Thrombosis and Haemostasis, 82(4), 1270-1275.

Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees. / Gu, Weikuan; Brooks, Marjory; Catalfamo, James; Ray, Jharna; Ray, Kunal.

In: Thrombosis and Haemostasis, Vol. 82, No. 4, 20.10.1999, p. 1270-1275.

Research output: Contribution to journalArticle

Gu, W, Brooks, M, Catalfamo, J, Ray, J & Ray, K 1999, 'Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees', Thrombosis and Haemostasis, vol. 82, no. 4, pp. 1270-1275.
Gu, Weikuan ; Brooks, Marjory ; Catalfamo, James ; Ray, Jharna ; Ray, Kunal. / Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees. In: Thrombosis and Haemostasis. 1999 ; Vol. 82, No. 4. pp. 1270-1275.
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