2004 Deafness Report from Dr. George M. Strain, Louisiana State University

JRTRF-funded research by Dr. George M. Strain (LSU Baton Rouge) has made significant progress in the short time it has been active. Although the prevalence of pigment-associated congenital nerve deafness in the Jack Russell terrier (approximately 13% are deaf in one or both ears) does not approach that of the Dalmatian breed (30%), it nevertheless is a hereditary disorder of concern within the breed. Current studies with the Dalmatian are seeking to identify the gene defect responsible for deafness using molecular genetics techniques. Although the inheritance appears to be complex, the chances of identifying it in the Dal are greater than in the JRT due to the higher disease prevalence.

The present JRT project was formulated with the knowledge that several leading labs (Texas A&M, Germany, Switzerland) are working to identify the
Dal gene defect, so that we will be prepared to address JRT deafness once progress has been made with the Dal. With the cooperation of many JRT breeders and owners, and coordination by Genie Franklin, we have been collecting DNA samples using cheek swabs from a large multi-generation pedigree of related dogs. We then plan to test this DNA against the findings from Dal studies to determine whether the same gene defect causes deafness in the JRT, or whether a different defect is responsible. It is by
far more likely to be the case that the same defect is causative, but we cannot assume this to be true. There are numerous examples in human and mouse genetics where the same disease "phenotype" is caused by more than one gene defect, sometimes even on different chromosomes. We don't even know for certain that only one defect occurs in a single dog breed!

The collected DNA samples of this study are being frozen and banked in preparation for the chance to compare the two breeds. To date, DNA samples have been collected from 158 JRT, most of whom are related; 24 of these are
deaf in one or both ears. We are presently working to fill in missing gaps and important individual animals.

We are uncertain as to when we will be able to actually test the JRT DNA, as that is contingent on progress with Dalmatian studies. Early Dal studies examined so-called "candidate" genes, genes shown in mice or humans to cause pigment-associated deafness, such as c-kit and mitf. When identified and sequenced in dog DNA, none of these candidate genes proved to be responsible for Dal deafness. The next approach was a whole-genome screen.

Numerous short stretches of DNA spread out over all of the dog's 39 chromosome pairs (the whole genome) at fairly regular spacing have been identified and published. These segments, usually of non-gene encoding DNA, are known as microsatellite markers. The beginning and end of these markers are the same from dog to dog, but there can be variation in the middle of the segment, known as a polymorphism ("many shapes"). Because a disease-causing gene defect may be close to a microsatellite marker, one of
the polymorphisms may be present in all dogs that have the defect as the two are likely to be inherited together. So the approach is to chop up the DNA using enzymes and identify the polymorphism of each microsatellite marker for each dog, and see if any polymorphism "co-segregates" with deafness. This is an enormous task. The first canine microsatellite marker set (MSS1) contains 178 markers. When a whole-genome screen was performed with these markers on DNA from about 200 related Dals, no marker polymorphism co-segregated with deafness, a disappointing finding. One marker did co-segregate with liver spot color, so the technique worked correctly -- the gene defect just wasn't located close enough to one of the markers to be detected. There is now available a new set of markers (MSS2) with 327 microsatellites, more closely spaced together, and that don't overlap the first set, so the next step is to perform a whole-genome screen with this set. Funds are currently being sought (~ $80K) to perform this work. Once a marker is found that co-segregates with deafness, the genes close to it will be identified and sequenced, and then compared in deaf and hearing dogs. The ultimate goal is to develop a DNA-based blood test to identify carriers, to better inform breeding decisions.

George M. Strain
Professor of Neuroscience
Comparative Biomedical Sciences
Louisiana State University School of Veterinary Medicine
Baton Rouge, LA 70803
Voice 225-578-9758
Fax 225-578-9895
Research: www.lsu.edu/deafness/deaf.htm