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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.

Incorporation of FISH Reference Clones, Genetic Markers and Genes into the Physical Map of Human Chromosome 19

Susan Tsujimoto, Annette Swartz, Laurie Gordon, Anthony V. Carrano, Brigitte Brandriff, and Harvey W. Mohrenweiser
Human Genome Center; L-452, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory; Livermore, California 94550.

The usefulness of a physical map is dependent on the number of attributes assigned to and positioned along that map. A densely populated physical map of ordered genes and genetic markers allows the map to be combined with other types of maps and data. Our cosmid contig map of human chromosome l9 covers 54 MB, ~95% of the non-centromeric region of the chromosome, and contains >200 genes, >50 ESTs, and >100 polymorphic markers, all of which have been assigned to cosmids that have been cytogenetically localized. Over 80 of the >100 currently available, highly informative genetic markers have been assigned to cosmids. Many of these markers were mapped to cosmids using a strategy that exploits the unique sequence on either side of a microsatellite repeat.

Of the localized genes and genetic markers assigned to cosmids, 160 of the markers, representing 120 contigs, have been incorporated into a detailed fluorescent in situ hybridization (FISH) order map. The order of and distance between cosmids was determined by FISH, using G1 interphase pronuclei of sperm as targets. The average distance between FISH mapped cosmids is ~250kb, and fewer than 15 gaps >500kb (maximum 800kb) remain to be resolved. The FISH ordered cosmids then served as anchor points amongst which an additional 60 markers from linkage and restriction fragment mapping data could be binned and ordered. A partial order tree generated by an automated computer algorithm incorporates these 220 markers, and serves as the backbone for our integration process of genetic and linkage information.

Discrepancies in the estimated physical and genetic distances are noted. The genetic distance between some markers is 15 times (15cM) the estimated physical distance (1MB); the total genetic distance is only ~2X the physical size of the chromosome. The currently available genetic markers are sufficient to provide a map with very few gaps greater than 1MB, although recombinational "hotspots" distort the linkage map.

Significant strides toward complete integration of the genetic and physical maps have been made. The commonality of reference points enhances the utility of our cosmid clone map of human chromosome l9 as a resource for positional cloning of disease genes and chromosome breakpoints or translocations.

This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract no. W-7405-ENG-48.