Published online 22 May 2006
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Structure-based prediction of insertion-site preferences of transposons into chromosomes
1 Department of Genetics, Cell Biology and Development, The Arnold and Mabel Beckman Center for Transposon Research, University of Minnesota Minneapolis, MN 55455, USA 2 Biomedical Sciences Graduate Program, University of California San Francisco San Francisco, CA 94143-0452, USA 3 Biostatistics Core, University of Minnesota Cancer Center Minneapolis, MN 55455, USA 4 University of Minnesota Cancer Center Minneapolis, MN 55455, USA
*To whom correspondence should be addressed at Department of Genetics, Cell Biology, and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA. Tel: +1 612 624 6736; Fax: +1 612 625 6140; Email: perry{at}cbs.umn.edu
Received January 29, 2006. Revised February 28, 2006. Accepted April 9, 2006.
Mobile genetic elements with the ability to integrate genetic information into chromosomes can cause disease over short periods of time and shape genomes over eons. These elements can be used for functional genomics, gene transfer and human gene therapy. However, their integration-site preferences, which are critically important for these uses, are poorly understood. We analyzed the insertion sites of several transposons and retroviruses to detect patterns of integration that might be useful for prediction of preferred integration sites. Initially we found that a mathematical description of DNA-deformability, called Vstep, could be used to distinguish preferential integration sites for Sleeping Beauty (SB) transposons into a particular 100 bp region of a plasmid [G. Liu, A. M. Geurts, K. Yae, A. R. Srinivassan, S. C. Fahrenkrug, D. A. Largaespada,J. Takeda, K. Horie, W. K. Olson and P. B. Hackett (2005) J. Mol. Biol., 346, 161–173 ]. Based on these findings, we extended our examination of integration of SB transposons into whole plasmids and chromosomal DNA. To accommodate sequences up to 3 Mb for these analyses, we developed an automated method, ProTIS©, that can generate profiles of predicted integration events. However, a similar approach did not reveal any structural pattern of DNA that could be used to predict favored integration sites for other transposons as well as retroviruses and lentiviruses due to a limitation of available data sets. Nonetheless, ProTIS© has the utility for predicting likely SB transposon integration sites in investigator-selected regions of genomes and our general strategy may be useful for other mobile elements once a sufficiently high density of sites in a single region are obtained. ProTIS analysis can be useful for functional genomic, gene transfer and human gene therapy applications using the SB system.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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