Development of genomic resources in the domestic cat is key to application of this species as a model for heritable and infectious diseases, and for comparative genome analysis. Previous versions of the cat gene map, based on somatic cell hybrid analysis, revealed considerable conservation of synteny with the human genome. However, these maps provided no knowledge of gene order and genome rearrangement between the two species, information that is critical to applying the comparative candidate approach to positional cloning in gene-poor model systems. Radiation hybrid (RH) mapping has emerged as the most powerful tool for constructing moderate- to high-density gene maps in vertebrates by obviating the need to identify interspecific polymorphisms. A domestic cat RH panel has been developed and serves as the backbone for feline gene mapping, while also serving to cross-reference microsatellite positions on the domestic cat linkage map. We are in the process of completing a fourth generation RH map of the cat, which nearly doubles our past cover of the cat genome. A fourth generation map has recently been completed; it includes 1793 markers, integrating 662 coding loci, 335 targeted markers derived from the cat 2X whole genome sequence, and 797 microsatellite loci. The strategy used in developing the current RH map was to target gaps in the feline-human comparative map, and to provide more definition in break points in regions of conserved synteny between cat and human. The 1793 markers cover the length of the 19 feline autosomes and the X chromosome at an average spacing of one marker every 1.5 Mb (Megabase), with fairly uniform marker density. The enhanced comparative map provides 86% and 85% comparative coverage of the human and canine genomes, respectively. Ninety-six percent of the 1793 cat markers have identifiable orthologues in the canine and human genome sequences, providing a rich comparative tool, which is critical in linkage mapping exercises for the identification of genes controlling feline phenotypes. Alignment of cat, dog and human chromosomes demonstrate different patterns of chromosomal rearrangement with a marked increase in interchromosomal rearrangements relative to humans in the canid lineage (89% of all rearrangements), as opposed to the more frequent intrachromosomal rearrangements in the felid lineage (95% of all rearrangements) since divergence from a common carnivoran ancestor 55 million years (MY) ago. With an average spacing of 1 marker every 1.5 Mb in the feline euchromatic sequence, the map provides a solid framework for the chromosomal assignment of feline contigs and scaffolds during assembly of the cat genome assembly and as a comparative tool to aid in the identification of genes controlling feline phenotypes. Most notable discovery: development of 4th generation map which demonstrated different patterns of chromosomal rearrangement with a marked increase in interchromosomal rearrangements relative to humans in the canid lineage (89% of all rearrangements), as opposed to the more frequent intrachromosomal rearrangements in the felid lineage (95% of all rearrangements) since divergence from a common carnivoran ancestor.No patents, clinical trials, grants, major appointments, or scientific awards.
| Murphy, William J; Pevzner, Pavel A; O'Brien, Stephen J (2004) Mammalian phylogenomics comes of age. Trends Genet 20:631-9 |
| Springer, Mark S; Murphy, William J; Eizirik, Eduardo et al. (2003) Placental mammal diversification and the Cretaceous-Tertiary boundary. Proc Natl Acad Sci U S A 100:1056-61 |
| Murphy, William J; Fronicke, Lutz; O'Brien, Stephen J et al. (2003) The origin of human chromosome 1 and its homologs in placental mammals. Genome Res 13:1880-8 |
| O'Brien, Stephen J; Murphy, William J (2003) Genomics. A dog's breakfast? Science 301:1854-5 |
| Kuznetsov, S B; Matveeva, N M; Murphy, W J et al. (2003) Mapping of 53 loci in American mink (Mustela vison). J Hered 94:386-91 |
| Murphy, William J; Bourque, Guillaume; Tesler, Glenn et al. (2003) Reconstructing the genomic architecture of mammalian ancestors using multispecies comparative maps. Hum Genomics 1:30-40 |
| Teeling, Emma C; Madsen, Ole; Murphy, William J et al. (2003) Nuclear gene sequences confirm an ancient link between New Zealand's short-tailed bat and South American noctilionoid bats. Mol Phylogenet Evol 28:308-19 |
