1601: Identifying the Genetic Cause of Fatal Neonatal Liver Disease

Grant Status: Closed

Grant Amount: $66,042
Peter A.J. Leegwater, PhD; University of Utrecht
January 1, 2012 - August 31, 2014

Sponsor(s): American Shih Tzu Club, Inc., English Setter Association of America, Inc., Estate of Christine Vachuska, National Beagle Club, Norwegian Elkhound Association of America, Inc., Papillon Club of America, Samoyed Club of America Education & Research Foundation, Soft Coated Wheaten Terrier Club of America, Inc., Soft Coated Wheaten Terrier Genetic Research Fund

Breed(s): Irish Wolfhound
Research Program Area: Hepatic Disease
Donate to Support this Research Program Area


Intrahepatic portosystemic shunt (IHPSS) is a liver disease caused by a failure to close a vessel that regulates blood flow from the placenta to vital organs like the lungs and heart during fetal development. This vessel should close within a few days after birth so that the liver is no longer bypassed by the vital portal blood flow. IHPSS leads to underdevelopment of the liver and severe (finally lethal) liver dysfunction. The condition is common in many large dog breeds. In this study, Irish wolfhounds will be used to identify the genetic cause of IHPSS. Pedigree analysis in this breed suggests that two genes act in concert to cause IHPSS. A large series of DNA samples from phenotypically characterized cases and controls will be used for genetic analysis. By comparing DNA variants between affected and healthy Irish wolfhounds, Dr. Leegwater will be able to select genomic regions which harbor the genes responsible for this severe liver disorder. The responsible mutations will then be identified by large scale DNA sequence analysis of these regions. Once gene mutations have been proven to cause IHPSS a DNA test can be developed to assist breeders in reducing the incidence of the disorder. In addition, with the available DNA of many large breed dogs diagnosed with IHPSS scientists will be able to immediately extrapolate findings to other large dog breeds.


van Steenbeek, F. G., Spee, B., Penning, L. C., Kummeling, A., van Gils, I. H. M., Grinwis, G. C. M., … Leegwater, P. A. J. (2013). Altered Subcellular Localization of Heat Shock Protein 90 Is Associated with Impaired Expression of the Aryl Hydrocarbon Receptor Pathway in Dogs. PLoS ONE, 8(3), e57973. https://doi.org/10.1371/journal.pone.0057973
van Steenbeek, F. G., Van den Bossche, L., Grinwis, G. C. M., Kummeling, A., van Gils, I. H. M., Koerkamp, M. J. A. Groot., … Spee, B. (2013). Aberrant Gene Expression in Dogs with Portosystemic Shunts. PLoS ONE, 8(2), e57662. https://doi.org/10.1371/journal.pone.0057662
van Steenbeek, F. G., van den Bossche, L., Leegwater, P. A. J., & Rothuizen, J. (2012). Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein. Mammalian Genome, 23(1–2), 76–84. https://doi.org/10.1007/s00335-011-9364-0

Help Future Generations of Dogs

Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.

Learn How to Help

Get Canine Health News:
Please leave this field empty
American Kennel Club Canine Health Foundation, Inc

8051 Arco Corporate Dr.
Suite 300
Raleigh, NC 27617

Tax ID# 13-3813813


© 2021 AKC Canine Health Foundation | Privacy Policy | Site Map

Site by Blackbaud, Inc.