Norman A. Doggett, Lynne A. Goodwin, Judith G. Tesmer, Linda J. Meincke, Michael R. Altherr, Amanda A. Ford, David C. Bruce, David C. Torney, Robert D. Sutherland, William J. Bruno, Emanual H. Knill, Grant R. Sutherland, David F. Callen, Larry L. Deaven, and Robert K. Moyzis.
Los Alamos National Laboratory, Los Alamos, NM, 87545
We have constructed an integrated map of human chromosome 16 (Doggett et al., Nature 377:Suppl:335-365, 1995). The framework for constructing this map is a high resolution cytogenetic breakpoint map derived from 78 mouse/human somatic cell hybrids and 4 fragile sites which divide chromosome 16 into 90 intervals of average size 1 Mb. The physical map consists of both a low resolution YAC contig map and a high resolution cosmid contig map. The low resolution YAC contig map is comprised of 700 CEPH megaYACs, and 250 flow-sorted 16 specific miniYACs that are localized to and ordered within the breakpoint intervals with 435 STSs. This YAC map provides practically complete coverage of the euchromatic arms of the chromosome.
A high resolution "sequence ready" cosmid contig map consisting of 4000 fingerprinted cosmids assembled into contigs covering 60% of the chromosome is anchored to the YAC and cytogenetic breakpoint maps via STSs developed from cosmid contigs and by hybridizations between YACs and cosmids. The largest of these cosmid contigs spans greater than 1 million base pairs of band 16p13.3 and has been used to initiate a sample sequencing (SASE) approach to gene localization on this chromosome (see abstracts of Ricke et al., Chi et al.).
A highly informative microsatellite-based genetic map (developed at the Adelaide Woman's and Children's Hospital) and the CEPH consortium linkage map is tightly integrated with the physical map--because nearly all of the genetic markers comprising these maps were either screened against the YAC map or localized to the cytogenetic breakpoint map.
An exon map consisting of 1000 distinct exons was recently developed from plate pools of the chromosome 16 cosmid library (see abstract of Altherr et al.). These exons are being mapped to cosmid contigs in the integrated map by hybridization of exons to cosmid grids. The integrated chromosome 16 map also includes over 600 genes, ESTs, anonymous DNA markers and microsatellite repeats--as part of an ongoing effort to incorporate all available GDB loci with the map. Supported by the US DOE under contract W-7405-ENG-36.
 Women's & Children's Hospital, Adelaide, Australia
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