Selection of target sites for mobile DNA integration in the human genome

被引:172
作者
Berry, Charles
Hannenhalli, Sridhar
Leipzig, Jeremy
Bushman, Frederic D. [1 ]
机构
[1] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA
[2] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, La Jolla, CA 92093 USA
[3] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA
关键词
D O I
10.1371/journal.pcbi.0020157
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
DNA sequences from retroviruses, retrotransposons, DNA transposons, and parvoviruses can all become integrated into the human genome. Accumulation of such sequences accounts for at least 40% of our genome today. These integrating elements are also of interest as gene-delivery vectors for human gene therapy. Here we present a comprehensive bioinformatic analysis of integration targeting by HIV, MLV, ASLV, SFV, L1, SB, and AAV. We used a mathematical method which allowed annotation of each base pair in the human genome for its likelihood of hosting an integration event by each type of element, taking advantage of more than 200 types of genomic annotation. This bioinformatic resource documents a wealth of new associations between genomic features and integration targeting. The study also revealed that the length of genomic intervals analyzed strongly affected the conclusions drawn - thus, answering the question "What genomic features affect integration?'' requires carefully specifying the length scale of interest.
引用
收藏
页码:1450 / 1462
页数:13
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