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

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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.

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Acknowledgements

Supported in part by the Verein Deutsche Drahthaar-Group North America and The Morris Animal Foundation. The authors thank Jacqueline Fremont and Lisa Spagnoletti for technical support and the referral veterinarians and owners of German wirehaired pointers who participated in the study.

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Authors and Affiliations

  1. Department of Population Medicine and Diagnostic Sciences, Comparative Coagulation Section, College of Veterinary Medicine, Cornell University, Upper Tower Road, Ithaca, NY 14853, USA

    Marjory B. Brooks

  2. The James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA

    Weikuan Gu, Jennifer L. Barnas, Jharna Ray & Kunal Ray

Authors
  1. Marjory B. Brooks
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  2. Weikuan Gu
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  3. Jennifer L. Barnas
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  4. Jharna Ray
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  5. Kunal Ray
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Correspondence to Marjory B. Brooks.

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Brooks, M.B., Gu, W., Barnas, J.L. et al. A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in dogs . Mamm Genome 14, 788–795 (2003). https://doi.org/10.1007/s00335-003-2290-z

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  • DOI: https://doi.org/10.1007/s00335-003-2290-z

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