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Nucleic Acids Research, 2002, Vol. 30, No. 2 e6
© 2002 Oxford University Press

A new approach to genome mapping and sequencing: slalom libraries

Veronika I. Zabarovska1, Rinat Z. Gizatullin2, Ali N. Al-Amin2, Raf Podowski2, Alexei I. Protopopov1,2, Sven Löfdahl3, Claes Wahlestedt2, Gösta Winberg1,3, Vladimir I. Kashuba1,2, Ingemar Ernberg1 and Eugene R. Zabarovsky1,2,4,*

1Microbiology and Tumor Biology Center and 2Center for Genomics Research, Karolinska Institute, 171 77 Stockholm, Sweden, 3Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden and 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 117 984 Moscow, Russia

We describe here an efficient strategy for simultaneous genome mapping and sequencing. The approach is based on physically oriented, overlapping restriction fragment libraries called slalom libraries. Slalom libraries combine features of general genomic, jumping and linking libraries. Slalom libraries can be adapted to different applications and two main types of slalom libraries are described in detail. This approach was used to map and sequence (with ~46% coverage) two human P1-derived artificial chromosome (PAC) clones, each of ~100 kb. This model experiment demonstrates the feasibility of the approach and shows that the efficiency (cost-effectiveness and speed) of existing mapping/sequencing methods could be improved at least 5–10-fold. Furthermore, since the efficiency of contig assembly in the slalom approach is virtually independent of length of sequence reads, even short sequences produced by rapid, high throughput sequencing techniques would suffice to complete a physical map and a sequence scan of a small genome.

* To whom correspondence should be addressed at: Microbiology and Tumor Biology Center, Karolinska Institute, 171 77 Stockholm, Sweden. Tel: +46 8 728 67 50; Fax: +46 8 31 94 70; Email: eugzab{at}ki.se


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