William J. Murphy
	Rank	Associate Professor
	Department	Veterinary Integrative Biosciences
	Phone	(979) 458-0906
	Fax	(979) 845-9972
	Email Address	wmurphy@cvm.tamu.edu

Creation of a high-density comparative map of the feline genome. The recent announcement by the NHGRI to produce a low coverage (2X) sequence assembly of the feline genome will require a mapping resource to fully cross reference this fragmented sequence to the human genome. We are developing high density gene maps of all cat chromosomes using radiation hybrid mapping. This resource is being applied towards comparative candidate positional cloning studies in feline pedigrees segregating phenotypes of interest for human and feline medicine.

Characterization and molecular evolution of genes involved in male fertility. We have established a series of Asian leopard cat x domestic cat pedigrees for examining differences in testis gene expression in sterile, subfertile and fertile backcross male offspring. These studies will identify candidate genes involved in feline fertility, their roles in reproductive isolation in felid species, and translation into effective breeding programs for exotic felids, which suffer from high incidences of abnormal sperm production. Recent studies suggest that the Y chromosome of different mammalian lineages has acquired many novel genes that enhance male reproductive function. We are also characterizing this unique yet important component of the feline genome to identify factors affecting feline fertility.

Comparative phylogenomic analysis of the cat genome. Developing genome maps of many mammalian species offers an opportunity to better understand the underlying relationship between genomic architecture and chromosomal rearrangement.  Specifically, these efforts are directed towards aligning multiple comparative maps from domestic and companion mammalian species, refining regions of conserved gene order and their breakpoints, and characterizing fragile regions of mammalian chromosomes towards understanding mechanisms of chromosome breakage and evolution. These studies will also quantify different types of genomic changes across lineages and applying this information to developing better models of genome evolution and to test hypotheses of random genome breakage and gene clustering constraining synteny.

Molecular Systematics of Mammals. Previous work in my lab and by others has established a well resolved superordinal hierarchy for placental mammals using large multigene concatenations. Other focused phylogenetic studies have used similar large molecular datasets of nuclear genes to resolve relationships of carnivores, bats, primates, and felids. However many aspects of mammalian interfamilial phylogeny remain unresolved, as well as the historical biogeography of these groups, and the integration of fossil taxa into molecular datasets. Current efforts will use a combination of tested nuclear markers and new genomic signatures to resolve the phylogeny of mammals.

Menotti-Raymond, M., David, V. A., Roelke-Parker, M., Sun, S., Shäffer, A., Agarwala, R., Tomlin, J.F., O'Brien, S. J. and W. J. Murphy.  2003.  Second generation integrated linkage and radiation hybrid maps of the domestic cat.  Journal of Heredity 94: 95-106.

Murphy, W. J., Fröenicke, L., O’Brien, S. J., and R. Stanyon. 2003. The origin of human chromosome 1 and its homologues in placental mammals. Genome Research 13: 1880-1888.

Roca, A. L., Kahila Bar-Gal, G., Eizirik, E., Helgen, K.M., Maria, R., Springer, M.S., O’Brien, S. J., and W. J. Murphy. 2004. Mesozoic origin for West Indian insectivores. Nature 429: 649-651.

Murphy, W. J., Pevzner, P. and S. J. O’Brien.  2004. Mammalian phylogenomics comes of age. Trends in Genetics 20: 631-639.