Construction of a physical map for human chromosome 19.

摘要

Unlike a genetic map which provides information on the relative position of genes or markers based upon the frequency of genetic recombination, a physical map provides a topographical picture of DNA, i.e. distances in base pairs between landmarks. The landmarks may be genes, gene markers, anonymous sequences, or cloned DNA fragments. Perhaps the most useful type of physical map is one that consists of an overlapping set of cloned DNA fragments (contigs) that span the chromosome. Once genes are assigned to this contig map, sequencing of the genomic DNA can be prioritized to complete the most interesting regions first. While, in practice, complete coverage of a complex genome in recombinant clones may not be possible to achieve, many gaps in a clone map may be closed by using multiple cloning vectors or uncloned large DNA fragments such as those separated by electrophoretic methods. Human chromosome 19 contains about 60 million base pairs of DNA and represents about 2% of the haploid genome. Our initial interest in chromosome 19 originated from the presence of three DNA repair genes which we localized to a region of this chromosome. Our approach to constructing a physical map of human chromosome 19 involves four steps: building a foundation of overlapping cosmid contigs; bridging the gaps in the cosmid map with hybridization-based methods to walk onto DNA cloned in yeast and cosmids: orienting the contigs relative to each other and linking them to the cytological map; and coupling the contig map with the genetic map. The methods we use and the current status of the map are summarized in this report. 6 refs., 1 fig.