The construction of a physical map for human chromosome 19 Page: 3 of 8
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THE CONSTRUCTION OF A PHYSICAL MAP FOR HUMAN
A.V. Carrano, J. Alleman, C. Amemiya, L.K. Ashworth, C. Aslanidis, E.W. Brans-
comb, J. Combs, C. Chen, M. Christensen, A. Copeland, A. Fertitta, E. Garcia, P.J.
de Jong, C. Kwan, J. Lamerdin, H. Mohrenweiser, A. Olsen, T. Slezak, B. Trask,
and K. Tynan
Human Genome Center, L-452, Biomedical Sciences Division, Lawrence Liver-
more National Laboratory, Livermore, CA 94550, U.S.A.
INTRODUCTION. Unlike a genetic map which provides information on the rela-
tive position of genes or markers based upon the frequency of genetic recombina-
tion, 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 sep-
arated by electrophoretic methods.
Human chromosome 19 contains about 60 million base pairs of DNA and rep-
resents 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: 1) building a foundation of overlapping cos-
mid contigs; 2) bridging the gaps in the cosmid map with hybridization-based
methods to walk onto DNA cloned in yeast and cosmids; 3) orienting the contigs
relative to each other and linking them to the cytological map; and 4) coupling the
contig map with the genetic map. This contig mapping approach is similar to the
approach that was used to create a physical map of C. elegans (1). The methods we
use and the current status of the map are summarized below.
CONTIG BUILDING. The source DNA for our cosmid library is derived from
chromosome 19 purified by flow sorting from a hamster-human hybrid cell line
containing chromosome 19 as the only human material (2). The cosmid library was
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Carrano, A.V.; Alleman, J.; Amemiya, C.; Ashworth, L.K.; Aslanidis, C.; Branscomb, E.W. et al. The construction of a physical map for human chromosome 19, article, November 5, 1990; [Livermore,] California. (https://digital.library.unt.edu/ark:/67531/metadc1108565/m1/3/: accessed April 21, 2019), University of North Texas Libraries, Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.