International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

D5 Human-Mouse Comparative Mapping of Human Chromosome 7

James W. Thomas, Tyrone J. Summers, D. Curtis Jamison, Shih-Queen Lee-Lin, Valerie V. Braden and Eric D. Green. National Human Genome Research Institute, NIH, Bethesda MD 20892

The success of the ongoing Human Genome Project has resulted in accelerated plans for completing the human genome sequence and the earlier-than-anticipated initiation of efforts to sequence the mouse genome. In recent years, our interests have focused on the systematic mapping and sequencing of human chromosome 7. As a complement to these activities, we have initiated a major program to map and sequence homologous regions of the mouse genome.

A framework human-mouse comparative map of human chromosome 7 was constructed by the traditional approach of identifying human-mouse orthologs that were mapped in both species. As an adjunct to this effort, we are actively using the available human chromosome 7 sequence to establish a more detailed comparative map. Specifically, genes not positioned on the chromosome 7 STS map are being routinely identified in chromosome 7 sequence and then precisely positioned relative to already-mapped STSs. Using this approach, we have been able to assign numerous genes to homologous positions in the mouse genome. Furthermore, these comparative markers can be used to predict the homologous location in the mouse genome of intervening human sequence.

In addition, the evolving human chromosome 7 sequence is being compared to all available mouse EST and gene sequences. Overgo probes are then derived from orthologous mouse sequences and used to screen the RPCI-23 mouse BAC library in a combinatorial screening strategy and to assemble BAC contigs based on probe-content data. Nascent contigs are then being extended with probes derived from BAC-end sequences.

This approach produces BAC-based sequence-ready maps known to contain a gene(s) and are homologous to segments of the human genome for which sequence is already available. Thus, the sequencing of these mouse clones will be of immediate interest for both their gene content as well as large-scale human-mouse sequence comparisons. To date, >299 overgos have been developed and used to assemble >1,750 clones into >50 contigs. Together, these contigs include at least 122 genes and ~10% of the mouse genome homologous to human chromosome 7. In conclusion, we are using newly available human genomic sequence as a resource to augment traditional comparative mapping, to facilitate the sequencing of the mouse genome, and to enhance our understanding of human chromosome 7 biology.

 


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