00640T: Linkage Disequilibrium Analysis of Markers Associated with Pug Dog Encephalitis

Grant Status: Closed

Grant Amount: $11,119.94
Dr. Kimberly A Greer, PhD, Indiana University East
July 1, 2008 - June 30, 2009
Breed(s): Pug
Research Program Area: Prevention

Project Summary

The research determined that there is no effect of geographical region of residence on the occurrence of PDE and that there is no seasonal effect associated with the development of PDE. Based on these results, they can now reasonably rule out seasonal allergens and temperature differences as environmental contributors to the development of PDE. When loooking at inheritance of the disease, the research found an inbreeding coefficient slightly higher than that for first cousin matings and slightly lower than that for uncle-niece or aunt-nephew mating. The overall result of high inbreeding is a significantly raised potential for lethal diseases in the breed. When looking closely at the dogs definitively diagnosed with PDE, it was found that more fawn female dogs get PDE than do other color and gender combinations. They did not find that PDE is being passed through the dogs in a standard straightforward Mendelian fashion, but were able to conclude that one significant genetic factor together with two or three modifier loci likely contribute to disease occurrence. As for environmental influences that may affect whether a dog gets the disease or not, the research was able to rule out known canine viruses including: parvovirus, herpesvirus, and adenovirus. None of the dogs affected with PDE had these viruses in their brains. The methods used to scan the whole genome for a location that may be contributing to PDE was extremely successful. The project identified a single marker location on canine chromosome 12 that is associated with the disease. The researchers interrogated the chromosomal region further by saturating the area with additional genetic markers. This portion of the study confirmed the previous data and demonstrated that the immunological portion of this chromosome is largely responsible for causing PDE. Within this region are the genes DRB, DQA, and DQB of DLA class II. Because all three genes are linked to one another, it was not able to decipher exactly which independent gene is contributing more significantly to disease; however, based on the genetic analysis the specific allele sequences will be able to be determine leading to a relative risk of association with disease (ie. a genetic test indicative of "high risk" for the disease).

Publication(s)

Greer, K.A., Lui H., Wong, A.K., Ruhe, A.L., Pedersen, N.C., Neff, M.W. 2009. Necrotizing Meningoencephalitis in the Pug Dog genetic association to DLAII DRQ-A and resemblance to multiple sclerosis. Science Translational Medicine (in preparation). Levine, J.M., G.T. Fosgate, B. Porter, S.J. Schatzberg, K.A. Greer. 2008. Epidemiology of necrotizing meningoencephalitis in Pug Dogs. Journal of Veterinary Internal Medicine 22(4): 961-968. Young, Bd, Levine, Jm, Fosgate, Gt, De Lahunta, A, Flegel, T, Matiasek, K, Miller, A, Silver, G, Sharp, N, Greer, K and Schatzberg, Sj (2009) Magnetic Resonance Imaging Characteristics of Necrotizing Meningoencephalitis in Pug Dogs. Journal of Veterinary Internal Medicine. 23, 527-35. http://dx.doi.org/10.1111/j.1939-1676.2009.0306.x Greer, K.A., S.J. Schatzberg, B.F. Porter, K.A. Jones, T.R. Famula, K.M. Murphy. 2008. Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug. Research in Veterinary Science. (http://dx.doi.org/10.1016/j.rvsc.2008.10.002)

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