title: Human l1 retrotransposition is associated with genetic instability in vivo.
abstract: Retrotransposons have shaped eukaryotic genomes for millions of years. To analyze the consequences of human L1 retrotransposition, we developed a genetic system to recover many new L1 insertions in somatic cells. Forty-two de novo integrants were recovered that faithfully mimic many aspects of L1s that accumulated since the primate radiation. Their structures experimentally demonstrate an association between L1 retrotransposition and various forms of genetic instability. Numerous L1 element inversions, extra nucleotide insertions, exon deletions, a chromosomal inversion, and flanking sequence comobilization (called 5' transduction) were identified. In a striking number of integrants, short identical sequences were shared between the donor and the target site's 3' end, suggesting a mechanistic model that helps explain the structure of L1 insertions.
authors.affiliation: Department of Molecular Biology and Genetics, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Symer
authors.forename: Carla
authors.initials: C
authors.lastname: Connelly
authors.forename: Suzanne T
authors.initials: ST
authors.lastname: Szak
authors.forename: Emerita M
authors.initials: EM
authors.lastname: Caputo
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cost
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D002213:Capsid / Q000096:biosynthesis / Q000235:genetics; D036022:Capsid Proteins; D004247:DNA / Q000032:analysis / Q000235:genetics; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D019143:Evolution, Molecular; D017353:Gene Deletion; D005809:Genes, Regulator / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D015894:Genome, Human; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics / Q000379:methods; D009154:Mutation / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D036022:Capsid Proteins; D006023:Glycoproteins; D009711:Nucleotides; D018626:Retroelements; D012313:RNA; D004247:DNA