Trends in Biotechnology
Volume 16, Issue 11, 1 November 1998, Pages 456-459
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Electronic PCR: bridging the gap between genome mapping and genome sequencing

https://doi.org/10.1016/S0167-7799(98)01232-3Get rights and content

Abstract

A crucial event in the history of the Human Genome Project was the decision to use sequence-tagged sites (STSs) as common landmarks for genomic mapping. Following several years of constructing STS-based maps of ever-increasing detail, the emphasis has recently shifted towards large-scale genomic sequencing. A computational procedure called `electronic PCR' allows STS landmarks to be revealed as data emerge from the sequencing pipeline, thereby bridging the gap between mapping and sequencing activities.

Section snippets

Genome mapping

For the first five years of its official existence, the Human Genome Project has focused on the construction of increasingly detailed physical maps of the genome. Two STS-based physical maps of the entire human genome have been developed, by the Whitehead Institute[4]and by the Stanford University Genome Center[5]. These maps are based partly (Whitehead) or entirely (Stanford) on radiation-hybrid (RH) methodology, in which the frequency of X-ray-induced DNA breakage between two STSs is used to

Genome sequencing

Although improvements to the maps are continuing, the past three years have seen a major shift in emphasis from mapping to sequencing. In the USA, the NIH has funded several genome centers to develop methodology for very-large-scale sequencing. In the UK, similar work is well under way at the Sanger Centre, with support from the Wellcome Trust. Additional genome-sequencing projects are evolving in Germany, France and Japan. Even though this renewed focus on sequencing is only a few years old, a

Bridging the gap

The common language of STSs provides the ability to correlate maps of ever-increasing resolution, and the use of e-PCR to detect STSs in DNA sequences carries this process to its ultimate conclusion. The map with highest possible resolution is the genomic sequence itself but, well in advance of assembling the final genomic reference sequence, localized regions can be brought into focus as they are completed. Within a sequenced region, exact base-pair distances between STSs can be determined.

Acknowledgements

Thanks to M. Boguski for his critical review of the manuscript. The software for constructing a composite sequence for a clone contig was provided by J. Zhang, who is also involved in maintaining the integrated human maps and sequences found in the Entrez Genomes division. The WWW resource for performing e-PCR was developed by S. Shavirin.

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