Characterization and Chromosomal Localization of Type I Loci of the Dog Keith Murphy, PhD  Texas A&M University

Summary:

It is clear that selective inbreeding of dogs has resulted in increased incidences of heritable diseases, especially those with an autosomal recessive mode of transmission. Importantly, detailed genetic and physical maps of the dog genome will provide the foundation for map-based positional cloning of genes that control various traits including some responsible for canine genetic diseases. Identification of specific genes and markers which co-segregate with clinical diseases will allow development of tests to identify both carriers and at-risk dogs. Such tests will accelerate elimination of disease alleles through more judicious breeding practices.

Mapping studies in model organisms (e.g., human and mouse) have relied on analyses of two types of loci in constructing genomic maps. Type I loci encode gene products, are conserved across mammalian genera and are useful for comparing linkage and syntenic relationships of similar genes among diverse animals. Type II loci are genomic regions that are highly polymorphic and generally exhibit species specificity. These include microsatellite markers and single-strand conformation polymorphisms. Analyses of type II loci can be used to greatly enhance understanding of the genetics of organisms; however, such heterogeneous markers are less useful for comparative genome studies because they are rarely conserved across species. Even so, the power of type 11 loci is clearly evident from the substantial progress that has been made toward the development of a canine linkage map using microsatellite repeats.

Our laboratories are interested in (1) characterizing genes required for development and which may be involved in the myriad of heritable diseases affecting the domestic dog and (2) contributing defined loci for placement on genetic and physical maps of the canine genome.

The approach we have taken is examination of conservation of the genetic organization, structure and function of known mammalian genes and gene families. Development of detailed genetic and physical maps of the domestic dog is a priority since such resources will facilitate study of the nearly 400 canine genetic diseases. Our interest is focused on those gene families implicated in developmental- processes and heritable diseases of the skin, eye, skeleton and, more recently, the ear of the domestic dog. Previous and ongoing work includes analyses of the transglutaminase I gene (tg1), the highly conserved keratin (krt) gene family, genes (bmp) that encode the bone morphogenetic proteins and the P450 gene family. Presented here are data describing isolation, sequence and chromosomal localization of canine genes we hypothesize are involved in heritable diseases of the dog. More specifically, results pertaining to the tgl, krt and bmp genes will be discussed. These results include (1) sequence data (2) chromosomal localization and (3) isolation of bacterial artificial chromosome clones and subsequent use in chromosomal localization experiments. Also to be addressed is the importance of the aforementioned genes in diseases of specific breeds.

Dr. Murphy's work is being supported by the following AKC Canine Health Foundation grants:

No. 1851 (Pending): Etiology of Corneal Indolent Ulcer in the Domestic Dog

No. 1870: Genetics of Hereditary Deafness in the Domestic Dog (sponsored in part by the Dalmatian Club of America Foundation)

Biographical Profile

Dr. Keith E. Murphy received his BS in Microbiology from Indiana University, and his MS in Molecular Genetics from the University of Cincinnati College of Medicine. After earning his PhD in Molecular Genetics from Louisiana State University, Dr. Murphy received postdoctoral training in cell biology and genetics at Northwestern University Medical School and the Arthropod-borne Animal Diseases Research Laboratory. Dr. Murphy is currently an Associate Professor of Veterinary Pathobiology at Texas A&M University College of Veterinary Medicine. He has also spent time on the faculties of The Citadel and The University of Memphis.

Work in his laboratory is designed to (1) identify and characterize genes responsible for heritable diseases of the dog, and (2) contribute to development of a detailed canine genome map through identification and chromosomal localization of type I loci.