title: Genomic deletions created upon LINE-1 retrotransposition.
abstract: LINE-1 (L1) retrotransposition continues to impact the human genome, yet little is known about how L1 integrates into DNA. Here, we developed a plasmid-based rescue system and have used it to recover 37 new L1 retrotransposition events from cultured human cells. Sequencing of the insertions revealed the usual L1 structural hallmarks; however, in four instances, retrotransposition generated large target site deletions. Remarkably, three of those resulted in the formation of chimeric L1s, containing the 5' end of an endogenous L1 fused precisely to our engineered L1. Thus, our data demonstrate multiple pathways for L1 integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA. gilbertn@umich.edu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gilbert
authors.forename: Sheila
authors.initials: S
authors.lastname: Lutz-Prigge
authors.forename: John V
authors.initials: JV
authors.lastname: Moran
mesh_terms: D001483:Base Sequence / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D017353:Gene Deletion; D005818:Genetic Engineering / Q000379:methods*; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D018626:Retroelements / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D018626:Retroelements