0001808A: An Integrated Linkage and Radiation Hybrid Map of the Dog: A Collaborative Project

Grant Status: Closed

Grant Amount: $148,892.95
Elaine A Ostrander, PhD; Fred Hutchinson Cancer Research Center
September 13, 1999 - September 12, 2001

Sponsor(s): Nestle Purina PetCare Company

Breed(s): -All Dogs
Research Program Area: General Canine Health
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Abstract

Genome maps or organisms are essential for locating and identifying genes that cause inherited disease. They consist of a series of markers, positioned along each chromosome, which act as reference points or address labels for different regions of the genome. Currently, the canine map is composed of about 400 such markers, which, in principal, provides "addresses" for about 75 percent of the genome. This early version of the map has proven useful for identifying the general location of disease genes in several breeds of dog. But a much more highly refined map is necessary if we are to have the ability to actually identify disease genes (not just their location) and to develop highly reproducible genetic tests for canine diseases. In addition, the current version of the map allows us to navigate around the genome only in relatively outbred pedigrees of dog. Many disease genes of interest are found in pedigrees or breeds where a limited gene pool has forced significant levels of inbreeding. A much higher resolution map with many additional markers is necessary to map disease genes within inbred families. This proposal aims to identify numerous additional markers and place them on the canine genome map. In addition, it aims to map many more genes on the map. Finally, it will link the evolving canine map to the more well developed maps of the human and mouse genomes. The resulting map will be useful for the identification of disease genes in all breeds of dog, and should allow canine geneticists to increase the rate at which they identify genes responsible for inherited diseases in the dog.

Publication(s)

Genomics, 84(3), 550–554. https://doi.org/10.1016/j.ygeno.2004.06.006
 
Mammalian Genome, 15(7). https://doi.org/10.1007/s00335-004-2365-5
 
Davis, B. W., & Ostrander, E. A. (2014). Domestic Dogs and Cancer Research: A Breed-Based Genomics Approach. ILAR Journal, 55(1), 59–68. https://doi.org/10.1093/ilar/ilu017
 
Gordon, D. (2003). Establishing Appropriate Genome-Wide Significance Levels for Canine Linkage Analyses. Journal of Heredity, 94(1), 1–7. https://doi.org/10.1093/jhered/esg009
 
Guyon, R., Lorentzen, T. D., Hitte, C., Kim, L., Cadieu, E., Parker, H. G., … Ostrander, E. A. (2003). A 1-Mb resolution radiation hybrid map of the canine genome. Proceedings of the National Academy of Sciences, 100(9), 5296–5301. https://doi.org/10.1073/pnas.0831002100
 
Hitte, C. (2003). Comparison of MultiMap and TSP/CONCORDE for Constructing Radiation Hybrid Maps. Journal of Heredity, 94(1), 9–13. https://doi.org/10.1093/jhered/esg012
 
Hitte, Christophe, Kirkness, E. F., Ostrander, E. A., & Galibert, F. (2008). Survey Sequencing and Radiation Hybrid Mapping to Construct Comparative Maps. Phylogenomics. Methods in Molecular Biology, 422, 65–77. https://doi.org/10.1007/978-1-59745-581-7_5
 
Hitte, Christophe, Madeoy, J., Kirkness, E. F., Priat, C., Lorentzen, T. D., Senger, F., … Galibert, F. (2005). Facilitating genome navigation: survey sequencing and dense radiation-hybrid gene mapping. Nature Reviews Genetics, 6(8), 643–648. https://doi.org/10.1038/nrg1658
 
Lingaas, F. (2003). A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Human Molecular Genetics, 12(23), 3043–3053. https://doi.org/10.1093/hmg/ddg336
 
Miller, A. B., Lowe, J. K., Ostrander, E. A., Galibert, F., & Murphy, K. E. (2001). Cloning, sequence analysis and radiation hybrid mapping of a mammalian KRT 2p gene. Functional & Integrative Genomics, 1(5), 305–311. https://doi.org/10.1007/s101420100038
 
Murphy, W. J. (2005). Dynamics of Mammalian Chromosome Evolution Inferred from Multispecies Comparative Maps. Science, 309(5734), 613–617. https://doi.org/10.1126/science.1111387
 
Quignon, P., Schoenebeck, J. J., Chase, K., Parker, H. G., Mosher, D. S., Johnson, G. S., … Ostrander, E. A. (2009). Fine Mapping a Locus Controlling Leg Morphology in the Domestic Dog. Cold Spring Harbor Symposia on Quantitative Biology, 74(0), 327–333. https://doi.org/10.1101/sqb.2009.74.009
 
Richman, M., Mellersh, C. S., André, C., Galibert, F., & Ostrander, E. A. (2001). Characterization of a minimal screening set of 172 microsatellite markers for genome-wide screens of the canine genome. Journal of Biochemical and Biophysical Methods, 47(1–2), 137–149. https://doi.org/10.1016/S0165-022X(00)00160-3
 
Sargan, D. R., Aguirre-Hernandez, J., Galibert, F., & Ostrander, E. A. (2007). An Extended Microsatellite Set for Linkage Mapping in the Domestic Dog. Journal of Heredity, 98(3), 221–231. https://doi.org/10.1093/jhered/esm006
 
Sutter, N. B., Bustamante, C. D., Chase, K., Gray, M. M., Zhao, K., Zhu, L., … Ostrander, E. A. (2007). A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Science, 316(5821), 112–115. https://doi.org/10.1126/science.1137045

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