selection of target sites for mobile dna integration in the human genome选择移动的目标站点集成在人类基因组dna.pdfVIP

Selection of Target Sites for Mobile DNA Integration in the Human Genome 1 2 3 3* Charles Berry , Sridhar Hannenhalli , Jeremy Leipzig , Frederic D. Bushman 1 Department of Family and Preventive Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America, 2 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 3 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America 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. Citation: Berry C, Hannenhalli S, Leipzig J, Bushman FD (2006) Selection of target sites for mobile DNA integration in the human genome. PLoS Comput Biol 2(11): e157. doi:10.1371/journal.pcbi.0020157 Introduction