TY - JOUR A1 - Thomas, James W. A1 - Summers, Tyrone J. A1 - Lee-Lin, Shih-Queen A1 - Maduro, Valerie V. Braden A1 - Idol, Jacquelyn R. A1 - Mastrian, Stephen D. A1 - Ryan, Joseph F. A1 - Jamison, D. Curtis A1 - Green, Eric D. T1 - Comparative Genome Mapping in the Sequence-based Era: Early Experience with Human Chromosome 7 Y1 - 2000/05/01 JF - Genome Research JO - Genome Research SP - 624 EP - 633 DO - 10.1101/gr.10.5.624 VL - 10 IS - 5 UR - http://genome.cshlp.org/content/10/5/624.abstract N2 - 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. As a complement to these efforts, we are utilizing the available human sequence to refine human-mouse comparative maps and to assemble sequence-ready mouse physical maps. Here we describe how the first glimpses of genomic sequence from human chromosome 7 are directly facilitating these activities. Specifically, we are actively enhancing the available human-mouse comparative map by analyzing human chromosome 7 sequence for the presence of orthologs of mapped mouse genes. Such orthologs can then be precisely positioned relative to mapped human STSs and other genes. The chromosome 7 sequence generated to date has allowed us to more than double the number of genes that can be placed on the comparative map. The latter effort reveals that human chromosome 7 is represented by at least 20 orthologous segments of DNA in the mouse genome. A second component of our program involves systematically analyzing the evolving human chromosome 7 sequence for the presence of matching mouse genes and expressed-sequence tags (ESTs). Mouse-specific hybridization probes are designed from such sequences and used to screen a mouse bacterial artificial chromosome (BAC) library, with the resulting data used to assemble BAC contigs based on probe-content data. Nascent contigs are then expanded using probes derived from newly generated BAC-end sequences. This approach produces BAC-based sequence-ready maps that are known to contain a gene(s) and are homologous to segments of the human genome for which sequence is already available. Our ongoing efforts have thus far resulted in the isolation and mapping of >3,800 mouse BACs, which have been assembled into >100 contigs. These contigs include >250 genes and represent ∼40% of the mouse genome that is homologous to human chromosome 7. Together, these approaches illustrate how the availability of genomic sequence directly facilitates studies in comparative genomics and genome evolution. ER -