title: Comparative genome mapping in the sequence-based era: early experience with human chromosome 7.
abstract: 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.
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Thomas
authors.forename: T J
authors.initials: TJ
authors.lastname: Summers
authors.forename: S Q
authors.initials: SQ
authors.lastname: Lee-Lin
authors.forename: V V
authors.initials: VV
authors.lastname: Maduro
authors.forename: J R
authors.initials: JR
authors.lastname: Idol
authors.forename: S D
authors.initials: SD
authors.lastname: Mastrian
authors.forename: J F
authors.initials: JF
authors.lastname: Ryan
authors.forename: D C
authors.initials: DC
authors.lastname: Jamison
authors.forename: E D
authors.initials: ED
authors.lastname: Green
mesh_terms: D000818:Animals; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D016045:Human Genome Project; D006801:Humans; D020161:Physical Chromosome Mapping / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*