An integrated physical/genetic/cytogenetic map of human chromosome 16

We have constructed an integrated physical/genetic/cytogenetic map of human chromosome 16. The framework for constructing this map is a high resolution cytogenetic breakpoint map derived from 77 mouse/human somatic cells hybrids which divide human chromosome 16 into 67 discernible intervals of average size 1.3 Mb. The physical map consists of both a low resolution YAC contig map and high resolution cosmid contig map. The low resolution YAC contig map is comprised of 450 CEPH Mega YACs and 200 flow-sorted 16-specific YACs that are localized to and ordered within each of the 67 breakpoint intervals with {approximately}300 STSs. This YAC map provides nearly complete coverage of the euchromatic arms of the chromosome. The high resolution cosmid contig map is anchored to the YAC map via STSs developed from cosmid contigs and by hybridization of YAC Alu-PCR products to cosmid grids. Previously, 4000 cosmids were fingerprinted and assembled into 550 cosmid contigs, providing 60% coverage of the chromosome in cosmid contigs and an additional 28% in singleton cosmids. A total of 300 of these cosmid contigs containing 1600 cosmids has been integrated with the physical/genetic/cytogenetic map and thus regionally localized along the chromosome. A highly informative microsatellite-based genetic map (developed at themore » Adelaide Women`s & Children`s Hospital), consisting of 78 PCR typeable markers and having a 2.6 cM median (3.2 average) distance between markers, is integrated with the physical and cytogenetic map in two ways: direct integration at the cosmid level because many of these GT/CA repeats were developed from localized cosmids or hybridized to cosmid grids, and by regional localization of all markers of the cytogenetic breakpoint map. This integrated map is facilitating the cloning of various disease genes and fragile sites on chromosome 16.« less