Faculty Collaboration Database

Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res 2006;34(9):2803-11

Date

05/24/2006

Pubmed ID

16717285

Pubmed Central ID

PMC1464413

DOI

10.1093/nar/gkl301

Scopus ID

2-s2.0-33744827138 (requires institutional sign-in at Scopus site)   65 Citations

Abstract

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 V(step), 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.

Author List

Geurts AM, Hackett CS, Bell JB, Bergemann TL, Collier LS, Carlson CM, Largaespada DA, Hackett PB

Author

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Algorithms
Animals
Chromosomes, Mammalian
DNA Transposable Elements
Gene Targeting
Genetic Vectors
Genomics
Introns
Mice
Proto-Oncogene Proteins B-raf
Retroviridae