GENETIC MAPPING RESOURCE FOR COMMON MAMMALIAN DISEASES

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DESCRIPTION (provided by applicant): Companion animals have been characterized for heritable human diseases; many do not have a mouse counterpart. To bridge the gap between human and mouse biology, genome projects have been initiated for companion animals, particularly for the cat and the dog. Biologically focused genome initiatives for these species would span the gap between mouse and man more efficiently. A focused gene mapping approach would remedy the smaller scale of these initiatives and allow the genomes of companion animals to unlock their biological secrets for human health and scientific advancement. It would also provide an invaluable tool and resources to researchers throughout the world. The investigator's long-range goal is to use knowledge of genetic diseases in companion animals to gain insight into the pathogenesis of comparable diseases in man. The objective of this application is to develop comparative genetic maps of the cat and dog by using a focused approach of mapping 500 genes known to have biological relevance and to identify 300 microsatellite markers associated with these genes. This focus will provide resources and facilitate the research of human and companion animal investigators who have interests in particular biological processes, simple or complex traits, and inherited or acquired diseases. The investigators will accomplish this task through three Specific Aims: 1) develop conserved primers for approximately 500 genes and screen for variation; 2) identify species-specific bacterial artificial chromosomes (BAC) clones for each gene to identify gene-associated microsatellites; and 3) gene variations and the gene-associated microsatellites will be genotyped in the appropriate mapping resources. Because this project will generate comparative maps focusing on diseases that are difficult to study in humans, human health will rapidly benefit from the biology of companion animals. Researchers studying these diseases in animals and humans will have a leap in resources, including candidate genes, linked markers for familial and population based associations, and large insert genomic BAC clones. The proposed research is significant because it will provide a framework map comparable to humans in three species that have complex and simple disease traits that plague humans.