A central activity of the ongoing human genome project is the construction of maps for all human chromosomes en route to the eventual elucidation of their complete DNA sequence. The major aims of the Physical Mapping Section is to establish and implement approaches for developing integrated and highly annotated physical maps of human chromosomes and to utilize the resulting information for studying important biological problems. Our general mapping paradigm involves the detection of PCR-based landmarks called sequence-tagged sites (STSs) within large (100,000 to >1,000,000 bp) fragments of DNA cloned into yeast artificial chromosomes (YACs). We have focused our attention on the 170megabase human chromosome 7. A set of over 2200 chromosome 7-specific STSs has been developed and used to analyze a collection of over 4000 YACs highly enriched for human chromosome 7 DNA. Cross referencing the STSs with the YACs has allowed the assembly of very large YAC contigs, some of which span over 50 Mb is length. The evolving physical map has also been rigorously integrated with the cytogenetic, genetic, and radiation hybrid maps of the chromosome. Analysis of the data indicates that upwards of 98% of the chromosome is accounted for in the existing set of 22 well-anchored YAC contigs. As we near completion of our first-generation YAC-based map of the chromosome, our emphasis has increasingly turned towards two important activities. First, we are actively placing large numbers of gene sequences onto the evolving contig maps. In turn, such information has allowed us to study regions of chromosome 7 associated with human genetic diseases, including retinitis pigmentosa, Williams syndrome, cerebral cavernous malformations, hereditary deafness, and several other disease loci. Second, we are actively using our initial set of maps to assemble the necessary clones that will be used to generate the complete sequence of the chromosome. The latter effort represents entry into the new phase of the Human Genome Project, where human chromosome sequencing will be the highest priority. It is our expectation that chromosome 7 will be among the first human chromosomes to be completely sequenced.
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