ANS 378 Animal Genetics
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Research Journal Report #01
10/07/04
Research Topic: Inheritance of a Single Locus Trait
Animal Species: Canine
Title of the Paper: Analysis of the 5’ region of the canine PAX3 gene and exclusion as a candidate for Dalmation deafness
Author(s): Brenig, B.; Pfeiffer, I.; Jaggy, A.; Kathmann, I.; Balzari, M.; Gaillard, C.; Dolf, G.
Abstract: The causative mutation in a gene related to hearing loss in Dalmations has been elusive. Because of its role in melanocyte migration and differentiation as integral component of the inner ear, we hypothesized that the canine PAX3 (paired box homeotic gene 3) gene could be a candidate for Dalmation deafness. Therefore, we isolated the canine PAX3 gene and searched for causative mutations within the coding region of important regulatory domains of PAX3. However, no mutations were identified when comparing the DNA sequences of healthy and affected dogs. These results were confirmed by a two-point linkage analysis in 203 Dalmations transmitting deafness. Our data clearly show that the canine PAX3 gene can be excluded as candidate for Dalmation deafness.
Keywords: CFA37, Dalmation, deafness, paired-box gene 3, Waardenburg syndrome
Reference: Brenig, B., I. Pfeiffer, A. Jaggy, I. Kathmann, M. Balzari, C. Gaillard, and G. Dolf. 2003. Analysis of the 5’ region of the canine PAX3 gene and exclusion as a candidate for Dalmation deafness. Anim. Gen. 34:47-50.
Dalmations, as a breed, are known to be prone to deafness, but the causative agent has yet to be discovered. It is speculated that the problem lies within the breed’s genetics, because the hearing status of the parents seems to have a bearing on their offspring’s hearing. The authors of this paper hypothesized that the genetic cause of this trait lay within the PAX3 (paired box homeotic gene 3) gene of the canines. They partially based this hypothesis on research showing that in the corresponding PAX3 gene of humans and mice, a mutation in exons 1-4 can cause similar disorders to that of Dalmation deafness. By analyzing these exons using DNA sequencing in healthy and affected dogs, they were able to compare the results and determine if the PAX3 gene was the source of the trait.
The purpose of this research was to try to find the genetic cause of deafness in Dalmations. By comparing genes of dogs with normal hearing to those with either unilateral or bilateral hearing loss, the authors determined whether the PAX3 gene had mutated to cause deafness. If their hypothesis was disproved, then one possible cause of the disorder could be eliminated.
The results of their research show that there were no mutations in exons 1-4 of the canine PAX3 gene. Taking this a step further, a two-point linkage analysis was performed using the microsatellite associated with intron 4 on the gene. The result of this test supported the previous findings of the sequence analyses done on the PAX3 gene. This gene does not affect deafness in Dalmations and therefore cannot be the causative agent.
Research such as this is highly important in locating the sources of genetic disorders. Even if the hypotheses are not always correct, the results may be just as critical. By eliminating the canine PAX3 gene as the cause of Dalmation deafness, we are one step closer to finding the gene that is the source for this disorder. By eliminating possibilities, the field can be narrowed down until the responsible gene can unequivocally be determined.
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