A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in dogs

Marjory B. Brooks, Weikuan Gu, Jennifer L. Barnas, Jharna Ray, Kunal Ray

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We undertook the biochemical and molecular characterization of hemophilia in a large pedigree of German wirehaired pointers. Males affected with hemophilia B had approximately 5% normal Factor IX coagulant activity and a proportional reduction of Factor IX protein concentration, indicative of a mild hemophilia B phenotype. Using Southern blot analyses and PCR amplification of genomic DNA, we discovered a large, 1.5-kb insertion in intron 5 of the Factor IX gene of an affected male. The insert consists of a 5′ truncated canine Line-1 followed by an approximately 200-bp 3′ poly (A) tract, flanked by a 15-bp direct repeat. The insert can be traced through at least five generations and segregates with the hemophilia B phenotype in this breed. This is the first description of a Factor IX mutation associated with mild hemophilia B in a non-human species and provides evidence for a recent Line-1 insertion event in the canine genome.

Original languageEnglish (US)
Pages (from-to)788-795
Number of pages8
JournalMammalian Genome
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2003

Fingerprint

Hemophilia B
Factor IX
Dogs
Genes
Canidae
Phenotype
Coagulants
Poly A
Nucleic Acid Repetitive Sequences
Hemophilia A
Pedigree
Southern Blotting
Introns
Genome
Polymerase Chain Reaction
Mutation
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

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A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in dogs. / Brooks, Marjory B.; Gu, Weikuan; Barnas, Jennifer L.; Ray, Jharna; Ray, Kunal.

In: Mammalian Genome, Vol. 14, No. 11, 01.11.2003, p. 788-795.

Research output: Contribution to journalArticle

Brooks, Marjory B. ; Gu, Weikuan ; Barnas, Jennifer L. ; Ray, Jharna ; Ray, Kunal. / A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in dogs. In: Mammalian Genome. 2003 ; Vol. 14, No. 11. pp. 788-795.
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