920: Genetic Basis of Polyneuropathy in Leonbergers
Grant Status: Closed
Grant Amount: $44,528
James R. Mickelson, PhD; University of Minnesota
January 1, 2008 - June 30, 2010
Sponsor(s):
Breed(s): Leonberger
Research Program Area: Neurology
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Project Summary
We are using the most current gene identification strategy enabled by the canine genome project, termed SNP chips, to find the chromosomal locations of gene(s) causing susceptibility to polyneuropathy in Leonberger dogs (LPN). The ultimate goal is to develop DNA-based tests for susceptibility to LPN that can be used in breeding decisions to help reduce its incidence and potentially for more specific therapies to address the condition. The good news is that with the outstanding help of the breed clubs in the US and in Europe sufficient samples for the SNP chip gene mapping experiments were obtained. Other good news is that we now have several good chromosomal locations for where LPN genes might lie. The less good news is that there are several possible chromosomal locations for these LPN genes that are all about equally likely at the present time. This muddies the picture and may make developing a clear LPN susceptibility test more difficult. Nevertheless, Research carried out at the University of Minnesota, the University of Bern, and the University of California San Diego, indicates that polyneuropathy is likely a group of several genetically distinct, but clinically similar diseases. We have mapped two major genetic risk loci and identified the causative mutation in one of these loci that we now term LPN1. Dogs being homozygous mutant (two copies of the mutation) for this mutation will typically develop neuropathy before they reach 3 years of age. Dogs heterozygous for this mutation (one copy of the mutation) might also develop mild clinical signs late in life, but they will most likely not develop severe disease. The identified LPN1 mutation appears to be responsible for approximately one third of the cases of polyneuropathy in Leonbergers. The other two thirds of cases are apparently caused by different genetic mutations.Publication(s)
Ekenstedt, K. J., Becker, D., Minor, K. M., Shelton, G. D., Patterson, E. E., Bley, T., … Mickelson, J. R. (2014). An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs. PLoS Genetics, 10(10), e1004635. https://doi.org/10.1371/journal.pgen.1004635
Pemberton, T. J., Choi, S., Mayer, J. A., Li, F.-Y., Gokey, N., Svaren, J., … Duncan, I. D. (2014). A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination. Glia, 62(1), 39–51. https://doi.org/10.1002/glia.22582
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