Published online 18 February 2004
Nucleic Acids Research, 2004, Vol. 32, No. 3 e35
© 2004 Oxford University Press
Unlocking hidden genomic sequence
Department of Mathematics, 1 Australian Genome Research Facility and 2 Institute of Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia
*To whom correspondence should be addressed. Tel: +61 7 3365 2309; Fax: +61 7 3365 1477; Email: j.keith1{at}mailbox.uq.edu.au
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
Despite the success of conventional Sanger sequencing, significant regions of many genomes still present major obstacles to sequencing. Here we propose a novel approach with the potential to alleviate a wide range of sequencing difficulties. The technique involves extracting target DNA sequence from variants generated by introduction of random mutations. The introduction of mutations does not destroy original sequence information, but distributes it amongst multiple variants. Some of these variants lack problematic features of the target and are more amenable to conventional sequencing. The technique has been successfully demonstrated with mutation levels up to an average 18% base substitution and has been used to read previously intractable poly(A), AT-rich and GC-rich motifs.
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