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Journal of Heredity Advance Access published online on June 15, 2005
Journal of Heredity, doi:10.1093/jhered/esi078
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© The American Genetic Association. 2005. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org.

Article

Exclusion of Urate Oxidase as a Candidate Gene for Hyperuricosuria in the Dalmatian Dog Using an Interbreed Backcross

N. Safra 1, G. V. Ling 2, R. H. Schaible 3, and D. L. Bannasch 1*

1 From the Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616
2 From the Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616
3 From the Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University West Lafayette, IN 47907

* To whom correspondence should be addressed.
D. L. Bannasch, E-mail: dlbannasch{at}ucdavis.edu


  Abstract

Hyperuricosuria, an autosomal recessive disorder, is characterized by high levels of uric acid in the urine of Dalmatian dogs. Whereas high levels of uric acid are known to be caused by the silencing of the urate oxidase (uox) gene in humans and higher primates, the molecular basis for the Dalmatian defect is unknown. Transplantation studies show that the organ responsible for the Dalmatian phenotype is the liver, which is where urate oxidase is exclusively expressed and uric acid is converted into allantoin. We cloned and sequenced the canine uox cDNA and compared the sequence between a Dalmatian and non-Dalmatian dog. No change in cDNA sequence was identified. A Dalmatian x pointer backcross family was used to track the segregation of microsatellite markers surrounding the urate oxidase locus. The uox gene was excluded for Dalmatian hyperuricosuria based on the cDNA sequence identity and negative LOD scores.


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