1601: Identifying the Genetic Cause of Fatal Neonatal Liver Disease

Grant Status: Closed

Grant Amount: $66,042
Dr. 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


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 FG, van den Bossche L, Leegwater PA, Rothuizen J.; Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein.; Mamm Genome. 2012 Feb;23(1-2):76-84. - Van Steenbeek FG, S

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