Sequence Ready—or Not?
- Department of Genetics and the Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri 63108 USA
This extract was created in the absence of an abstract.
En route to the goal of the Human Genome Project (HGP) of obtaining the complete sequence of the human genome by the year 2005, several milestones have been reached (Collins and Galas 1993). First was the construction of a genetic linkage map with an average resolution of 1 cM (Dib et al. 1996). Second was the construction of a physical map with an average marker spacing of <150 kb (Hudson et al. 1995). These are laudable achievements; however, they only represent the completion of the initial phase of generating a sequence-ready physical map of the human genome that will provide the necessary templates for large-scale sequencing.
The current physical map is composed of two main resources. The first is physical maps made up of overlapping cloned fragments of human DNA. These clone contigs have been largely constructed using sequence-tagged site (STS) content mapping methods (Green and Olson 1990). The most comprehensive human genome physical maps are largely composed of overlapping yeast artificial chromosome [(YAC) Burke et al. 1992] clones [see http://www-genome.wi.mit.edu (Cohen et al. 1993; Chumakov et al. 1995; Hudson et al. 1995)]. Unfortunately, YAC clones are not suitable substrates for large-scale sequencing of the human genome. This is largely due to the high rate of chimaerism, the high frequency of deletions and rearrangements observed in these clones, and the difficulty of obtaining purified YAC DNA. The second physical map resource that is widely used is the whole-genome radiation hybrid (RH) map (Hudson et al. 1995; Schuler et al. 1996;Stewart et al. 1997). This map provides many additional ordered and binned markers and …
