Automated Construction of Comparative Maps between Zebrafish, Human, Rat and Mouse

Jedidiah Mathis1, Victor Ruotti2, Jeff Nie, Dan Chen, John Postlethwait, Monte Westerfield, Michael Thomas, Michael Carvan, Peter Tonellato, Medical College of Wisconsin;, Medical College of Wisconsin

Over the last 200 years, animal models have been selected and used as surrogates for humans, their primary criteria for selection being human-like disease characteristics from rat, mouse and now zebrafish. According to the Krogh principle, for many problems, there will be an animal in which it is most conveniently studied. The idea that genomic organization also tends to be conserved between species were postulated in the early twentieth century, eventually leading to the generation of comparative genome maps between species. The emergence of the radiation hybrid (RH) maps in human, rat, mouse and zebrafish coupled with the development and RH mapping of large numbers of expressed sequence tags (ESTs) and their organization into UniGene clusters, has revolutionized the way comparative maps are built and maintained. We have used publicly available rat, mouse, human, and zebrafish data to identify genes and ESTs with interspecies sequence identity (predicted homology), identified their UniGene relationships, and incorporated their RH and genetic map positions to build completely integrated comparative maps which allows the researcher to generate comparisons between rat, mouse, human, and zebrafish. VCMap uses information from previously mapped genes in humans, mice, and/or rats to predict which genes lie between mapped genes in the zebrafish genome based on conserved synteny. The generation of these maps is iterative and labor-intensive because new maps, ESTs, and UniGene rebuilds are continuously produced. Therefore, we have developed a series of computer tools based on our algorithm that identifies UniGene anchors between rat, human, mouse, and zebrafish to develop and annotate the comparative map information, and to build and produce comparative framework maps in printable and on-line clickable formats that link the maps to a wide variety of useful data tools and databases. The maps have been developed and constructed using sequence-based comparisons, creating “hooks” for further sequence-based annotation of finished human, mouse, rat, and zebrafish sequence.