00578-A: Optimization of a DNA Test for the Deletion Mutation in MURR1 Causing Copper Toxicosis in Bedlington Terriers
Grant Status: Closed
Grant Amount: $12,733
Dr. Nigel Holmes,, Animal Health Trust
July 1, 2005 - September 30, 2005
Breed(s): Bedlington Terrier
Abstract Copper toxicosis in Bedlington Terriers is an autosomal recessive condition characterized by high levels of hepatic copper. The disease usually leads to liver damage and cirrhosis. Most Bedlington populations show a high incidence for this condition. Testing is currently carried out by histological examination and measurement of copper levels in liver biopsies (for affected dogs) or by using a microsatellite marker (C04107) in a PCR-based test. Uncertainties in interpretation of these tests make development of a DNA-based test detecting the causative mutation a priority. Recent studies identified the mutation as a deletion of exon 2 in the gene MURR1 and also showed that C04107 is situated within intron 1 of this gene. Research at the Animal Health Trust has subsequently characterized the mutation precisely and will provide the basis for developing a new test. We propose a limited study to develop a robust diagnostic test from our research data on MURR1. PCR multiplexes developed for research will be adapted for use on an ABI 3100 sequencer for high-throughput routine testing. The testing protocol will be optimized using a set of samples from dogs which we have already typed for C04107, containing a representative mix of C04107 genotypes.