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Structure-based prediction of insertion-site preferences of transposons into chromosomes

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,...

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Autores principales: Geurts, Aron M., Hackett, Christopher S., Bell, Jason B., Bergemann, Tracy L., Collier, Lara S., Carlson, Corey M., Largaespada, David A., Hackett, Perry B.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1464413/
https://www.ncbi.nlm.nih.gov/pubmed/16717285
http://dx.doi.org/10.1093/nar/gkl301
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author Geurts, Aron M.
Hackett, Christopher S.
Bell, Jason B.
Bergemann, Tracy L.
Collier, Lara S.
Carlson, Corey M.
Largaespada, David A.
Hackett, Perry B.
author_facet Geurts, Aron M.
Hackett, Christopher S.
Bell, Jason B.
Bergemann, Tracy L.
Collier, Lara S.
Carlson, Corey M.
Largaespada, David A.
Hackett, Perry B.
author_sort Geurts, Aron M.
collection PubMed
description 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.
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spelling pubmed-14644132006-05-26 Structure-based prediction of insertion-site preferences of transposons into chromosomes Geurts, Aron M. Hackett, Christopher S. Bell, Jason B. Bergemann, Tracy L. Collier, Lara S. Carlson, Corey M. Largaespada, David A. Hackett, Perry B. Nucleic Acids Res Article 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. Oxford University Press 2006 2006-05-22 /pmc/articles/PMC1464413/ /pubmed/16717285 http://dx.doi.org/10.1093/nar/gkl301 Text en © The Author 2006. Published by Oxford University Press. All rights reserved
spellingShingle Article
Geurts, Aron M.
Hackett, Christopher S.
Bell, Jason B.
Bergemann, Tracy L.
Collier, Lara S.
Carlson, Corey M.
Largaespada, David A.
Hackett, Perry B.
Structure-based prediction of insertion-site preferences of transposons into chromosomes
title Structure-based prediction of insertion-site preferences of transposons into chromosomes
title_full Structure-based prediction of insertion-site preferences of transposons into chromosomes
title_fullStr Structure-based prediction of insertion-site preferences of transposons into chromosomes
title_full_unstemmed Structure-based prediction of insertion-site preferences of transposons into chromosomes
title_short Structure-based prediction of insertion-site preferences of transposons into chromosomes
title_sort structure-based prediction of insertion-site preferences of transposons into chromosomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1464413/
https://www.ncbi.nlm.nih.gov/pubmed/16717285
http://dx.doi.org/10.1093/nar/gkl301
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