Introduction to the Workshop
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The electronic form of this document may be cited in the following style:
Human Genome Program, U.S. Department of Energy, DOE Human Genome Program Contractor-Grantee Workshop IV, 1994.
Abstracts scanned from text submitted for November 1994 DOE Human Genome Program Contractor-Grantee Workshop. Inaccuracies have not been corrected.
DETAILED MAN-MOUSE COMPARATIVE MAPS OF HUMAN CHROMOSOME 19
[1,6]Johannah Doyle, Estela Generoso, William Dunn, Beverly Stanford, Ethan Carver, Eugene Rinchik, Susan Watt, Wolfgang Zimmermann, Linda Ashworth, Greg Lennon, Anne Olsen, Susan Tsujimoto, Harvey Mohrenweiser, Brigitte Brandriff and Lisa Stubbs
Mammalian Genetics and Development Section, Biology Division, Oak Ridge National Laboratory, P.O. Box 2009, Oak Ridge, TN 37831-8077; Sarah Lawrence College, 1 Mead Way, Bronxville, NY 10708; MRC Molecular Haematology Unit, John Radcliffe Hospital, Oxford OX3 9DU, UK; Dept. Immunobiology, University of Freiburg, Freiburg, Germany; Human Genome Center, Lawrence Livermore National Laboratory, P.O. Box 808, L-452, Livermore, CA 94551; Corresponding Author.
In order to set the stage for the exploitation of the mouse in the functional analysis of human chromosome 19, we have constructed series of detailed maps of related regions of the mouse genome. We have initiated these efforts by systematically localizing more than fifty conserved human chromosome 19 markers on the genetic map of the mouse, most representing genes that serve as regional anchors on LLNL's highly detailed physical map. Because both maps are centered upon the same series of markers, and because all murine markers have been mapped on a single interspecies backcross system, these data provide a measure of accuracy and internal consistency that is lacking from most published consensus maps. The large number and high density of markers that have now been genetically assigned to conserved regions has provided the foundation for initiation of physical maps in regions of special interest, allowing synteny relationships to be examined on the detailed molecular level.
While homologs of 19p genes are split into relatively small homology segments on several different mouse chromosomes (8, 9, 10 and 17), the entire length of 19q is represented within a 25 cM region of proximal mouse chromosome 7. Our results show that related genes are organized in a remarkably similar fashion along the lengths of these large, homologous regions, although with a few notable exceptions. A 4-5 Mb gene-rich region of human chromosome 19q13.3-13.4, for example, appears to have been 'transposed' from its relatively telomeric position to a murine region that is most closely related to the centromeric portion of the human chromosome; mouse equivalents of the clustered human PSG (pregnancy-specific glycoprotein) genes of human 19q13.2 are also located in completely different genomic environments in mouse and man. Both the similarities and the differences provide important insights regarding the evolution of this gene-rich human chromosome, and provide a powerful basis for the application of ES cell-based and molecular methods for assessing the functions of resident genes.
This work was supported by USDOE under contract DE-AC0584OR21400 with Martin Marietta Energy Systems, Inc., and contract W-7405-ENG-48 with the Lawrence Livermore National Laboratory.