Comparative genome mapping in the sequence-based era: early experience with human chromosome 7

• Published in: Genome research Vol. 10; no. 5; pp. 624 - 633
• Main Authors: Thomas, J W, Summers, T J, Lee-Lin, S Q, Maduro, V V, Idol, J R, Mastrian, S D, Ryan, J F, Jamison, D C, Green, E D
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.05.2000
• Subjects: Animals; Chromosomes, Human, Pair 7 - genetics; Human Genome Project; Humans; Physical Chromosome Mapping - methods; Sequence Analysis, DNA - methods
• ISSN: 1088-9051; 1549-5469
• DOI: 10.1101/gr.10.5.624

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 approximately 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.