title: L1 retrotransposition can occur early in human embryonic development.
abstract: L1 elements are autonomous retrotransposons that can cause hereditary diseases. We have previously identified a full-length L1 insertion in the CHM (choroideremia) gene of a patient with choroideremia, an X-linked progressive eye disease. Because this L1 element, designated L1(CHM), contains two 3'-transductions, we were able to delineate a retrotransposition path in which a precursor L1 on chromosome 10p15 or 18p11 retrotransposed to chromosome 6p21 and subsequently to the CHM gene on chromosome Xq21. A cell culture retrotransposition assay showed that L1(CHM) is one of the most active L1 elements in the human genome. Most importantly, analysis of genomic DNA from the CHM patient's relatives indicated somatic and germ-line mosaicism for the L1 insertion in his mother. These findings provide evidence that L1 retrotransposition can occur very early in human embryonic development.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: José A J M
authors.initials: JA
authors.lastname: van den Hurk
authors.forename: Iwan C
authors.initials: IC
authors.lastname: Meij
authors.forename: Maria del Carmen
authors.initials: MC
authors.lastname: Seleme
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kano
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Nikopoulos
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: de Wijs
authors.forename: Arijit
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Plomp
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D015794:Choroideremia / Q000235:genetics* / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6; D041321:Chromosomes, Human, X; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D009030:Mosaicism; D010375:Pedigree; D018626:Retroelements / Q000235:genetics*
chemical_list: D018626:Retroelements