Informatics Support for Mapping in Mouse-Human Homology Regions

Sergey Petrov, Manesh Shah, Loren Hauser[1], Richard Mural[1], and Edward Uberbacher

Computer Science and Mathematics Division and Biology Division[1], Oak Ridge National Laboratory, Oak Ridge, TN 37831-6364. 423/574-6134.

The purpose of this project is to develop databases and tools for the ORNL Mouse-Human Mapping Project, including the construction of a mapping database for the project, tools for management and archiving of cDNAs and other probes used in the laboratory, and analysis tools for mapping, interspecific backcross, and other needs. A re-evaluation of the needs of the Mouse-Human comparative mapping project has led us to implement an ACeDB based database for the management and display of the diverse mapping information associated with the project. Our choice of ACeDB for this task was based on the fact that the structure of the database and the organization of the raw data are clear and intuitive, and because it is being used as the data management system for a number of genome projects. Our ACeDB implementation has been modeled somewhat from the chromosome 21 ACeDB system at LBL (with some model modification) and is designed to contain genetic and physical mouse map data as well as homologous human chromosome data. The utility of exchanging map information with LLNL (human chromosome 19) and potentially other centers has led to the implementation of procedures for data export, and import of human mapping data into the ORNL databases.

Some examples of the information found in the current database are:

1. Many markers, both mouse and human, have been mapped to Mmu7 using one of two large interspecific backcrosses (M. spretus X M. musculus) created in the laboratory of Dr. Eugene Rinchik. The maps derived from these studies can be displayed in ACeDB and detailed information about the various marker can easily be accessed through this interface. In addition other genetic and physical maps in the system, a map of the homologous region of human chromosome l9q for example, can be directly compared to the genetic map of Mmu7 using the MultiMap feature of ACeDB.

2. The region around the murine p locus which correspond to the Prader-Willi/Angelman Syndrome region of human 15q, has been extensively studied at Oak Ridge over the last four decades. This has led to a wealth of both physical and genetic data which has been incorporated into the current database and which can be viewed and accessed through the ACeDB interface.

3. A genetic map of Mmu7 based on simple-repeat polymorphisms generated at MIT has been added to the database along with a MultiMap comparing it to the Oak Ridge IB map of Mmu7. This is a step toward integrating data being generated in other parts of the mouse community with the information being generated at Oak Ridge.

User access to the system is being provided by workstation forms-based data entry and ACeDB graphical data browsing. We have also implemented the LLNL databases browser to view the human chromosome 19 data maintained at LLNL, and arrangements are being made to incorporate mouse mapping information into the browser. Other applications such as the "Encyclopedia of the Mouse", specific tools for archiving and tracking cDNAs and other mapping probes, and analysis of inter-specific backcross data and restriction mapping of YACs have been implemented.

(Research sponsored by the Office of Health and Environmental Research, U.S. Department of Energy, under contract DE-AC05-840R21400 with Lockheed Martin Energy Systems, Inc.)