L1 retrotransposition can occur early in human embryonic development
Open accessAbstract
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.
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Evidence for L1 retrotransposition during early embryogenesis has been reported in humans.
“Evidence for L1 retrotransposition during early embryogenesis has also been reported in humans, (Brouha et al., 2002; van den Hurk et al., 2007).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as van den Hurk et al., 2007
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Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
A simple salting out procedure for extracting DNA from human nucleated cells
Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.3.1215 · Cited by 20,341 · see citing works
Mobile Elements: Drivers of Genome Evolution
Kazazian, H. H. (2004) · Science · doi:10.1126/science.1089670 · Cited by 1,922 · see citing works
Self-citationThe UCSC Genome Browser Database
Karolchik, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg129 · Cited by 1,887 · see citing works
Hot L1s account for the bulk of retrotransposition in the human population
Brouha, B., Schustak, J., Badge, R. M., Lutz-Prigge, S., Farley, A. H., Moran, J. V., & Kazazian, H. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0831042100 · Cited by 1,073 · see citing works
Self-citationSomatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition
Muotri, A. R., Chu, V. T., Marchetto, M. C. N., Deng, W., Moran, J. V., & Gage, F. H. (2005) · Nature · doi:10.1038/nature03663 · Cited by 942 · see citing works
Biology of Mammalian L1 Retrotransposons
Ostertag, E. M., & Kazazian, H. H. (2001) · Annual Review of Genetics · doi:10.1146/annurev.genet.35.102401.091032 · Cited by 764 · see citing works
Self-citationExon Shuffling by L1 Retrotransposition
Moran, J. V., DeBerardinis, R. J., & Kazazian, H. H. (1999) · Science · doi:10.1126/science.283.5407.1530 · Cited by 629 · see citing works
Self-citationDisruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.
Miki, Y., Nishisho, I., Horii, A., Miyoshi, Y., Utsunomiya, J., Kinzler, K. W., Vogelstein, B., & Nakamura, Y. (1992) · PubMed · Cited by 570 · see citing works
Human L1 element target‐primed reverse transcription in vitro
Cost, G. J., Feng, Q., Jacquier, A., & Boeke, J. D. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf592 · Cited by 519 · see citing works
DNA repair mediated by endonuclease-independent LINE-1 retrotransposition
Morrish, T. A., Gilbert, N., Myers, J. S., Vincent, B. J., Stamato, T. D., Taccioli, G. E., Batzer, M. A., & Moran, J. V. (2002) · Nature Genetics · doi:10.1038/ng898 · Cited by 488 · see citing works
Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes
Han, J. S., Szak, S. T., & Boeke, J. D. (2004) · Nature · doi:10.1038/nature02536 · Cited by 484 · see citing works
Human L1 Retrotransposition Is Associated with Genetic Instability In Vivo
Symer, D. E., Connelly, C. J., Szak, S. T., Caputo, E. M., Cost, G. J., Parmigiani, G., & Boeke, J. D. (2002) · Cell · doi:10.1016/s0092-8674(02)00839-5 · Cited by 479 · see citing works
Genomic Deletions Created upon LINE-1 Retrotransposition
Gilbert, N., Lutz-Prigge, S., & Moran, J. V. (2002) · Cell · doi:10.1016/s0092-8674(02)00828-0 · Cited by 474 · see citing works
Positional cloning of the gene for X-linked retinitis pigmentosa 2
Schwahn, U., Lenzner, S., Dong, J., Feil, S., Hinzmann, B., van Duijnhoven, G., Kirschner‐Schwabe, R., Hemberger, M., Bergen, A. A. B., Rosenberg, T., et al. (1998) · Nature Genetics · doi:10.1038/1214 · Cited by 384 · see citing works
Self-citationOrigin of the human L1 elements: Proposed progenitor genes deduced from a consensus DNA sequence
Scott, A. F., Schmeckpeper, B. J., Abdelrazik, M., Comey, C., O’Hara, B. F., Rossiter, J. P., Cooley, T., Heath, P. J., Smith, K. D., & Margolet, L. (1987) · Genomics · doi:10.1016/0888-7543(87)90003-6 · Cited by 313 · see citing works
L1 (LINE-1) Retrotransposon Evolution and Amplification in Recent Human History
Boissinot, S., Chevret, P., & Furano, A. V. (2000) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a026372 · Cited by 312 · see citing works
Determination of L1 retrotransposition kinetics in cultured cells
Ostertag, E. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.6.1418 · Cited by 291 · see citing works
Frequent Human Genomic DNA Transduction Driven by LINE-1 RetrotranspositionPreprint
Pickeral, O. K., Makałowski, W., Boguski, M. S., & Boeke, J. D. (2000) · Genome Research · doi:10.1101/gr.10.4.411 · Cited by 279 · see citing works
Transduction of 3'-flanking sequences is common in L1 retrotransposition
Goodier, J. L. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.4.653 · Cited by 266 · see citing works
Holmes, S. E., Dombroski, B. A., Krebs, C. M., Boehm, C. D., & Kazazian, H. H. (1994) · Nature Genetics · doi:10.1038/ng0694-143 · Cited by 231 · see citing works
Self-citationHeckenlively, J. R. (1987) · Cited by 229 · see citing works
Chen, J., Stenson, P. D., Cooper, D. N., & Férec, C. (2005) · Human Genetics · doi:10.1007/s00439-005-1321-0 · Cited by 226 · see citing works
LINE-1 retrotransposition in human embryonic stem cells
Garcia-Perez, J. L., Marchetto, M. C., Muotri, A. R., Coufal, N. G., Gage, F. H., O’Shea, K. S., & Moran, J. V. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm105 · Cited by 218 · see citing works
Eng, C., & Mulligan, L. M. (1997) · Human Mutation · doi:10.1002/(sici)1098-1004(1997)9:2 · Cited by 212 · see citing works
A mouse model of human L1 retrotransposition
Ostertag, E. M., DeBerardinis, R. J., Goodier, J. L., Zhang, Y., Yang, N., Gerton, G. L., & Kazazian, H. H. (2002) · Nature Genetics · doi:10.1038/ng1022 · Cited by 188 · see citing works
Self-citationKimberland, M. L., Divoký, V., Prchal, J. T., Schwahn, U., Berger, W., & Kazazian, H. H. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.8.1557 · Cited by 173 · see citing works
Self-citationEvidence consistent with human L1 retrotransposition in maternal meiosis I
Brouha, B., Meischl, C., Ostertag, E., de Boer, M., Zhang, Y., Neijens, H., Roos, D., & Kazazian, H. H. (2002) · The American Journal of Human Genetics · doi:10.1086/341722 · Cited by 122 · see citing works
Self-citationvan den Hurk, J. A. J. M., van de Pol, D. J. R., Wissinger, B., van Driel, M. A., Hoefsloot, L. H., de Wijs, I. J., van den Born, L. I., Heckenlively, J. R., Brunner, H. G., Zrenner, E., et al. (2003) · Human Genetics · doi:10.1007/s00439-003-0970-0 · Cited by 106 · see citing works
Self-citationSeleme, M. D. C., Vetter, M. R., Cordaux, R., Bastone, L. A., Batzer, M. A., & Kazazian, H. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601324103 · Cited by 104 · see citing works
Self-citationTracking an embryonic L1 retrotransposition event
Prak, E. T. L., Dodson, A. W., Farkash, E. A., & Kazazian, H. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337627100 · Cited by 97 · see citing works
Self-citationThe Abundant LINE-1 Family of Repeated DNA Sequences in Mammals: Genes and PseudogenesPreprint
Skowroński, J., & Singer, M. (1986) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1986.051.01.055 · Cited by 65 · see citing works
A highly polymorphic microsatellite marker located within the choroideremia gene
van Bokhoven, H., van den Hurk, J. A. J. M., Bogerd, L., et al. (1996) · Ophthalmic Genetics · doi:10.3109/13816819609057115 · Cited by 3 · see citing works
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L1 retrotransposition in human neural progenitor cells
Coufal, N. G., Garcia-Perez, J. L., Peng, G. E., Yeo, G. W., Mu, Y., Lovci, M. T., Morell, M., O’Shea, K. S., Moran, J. V., & Gage, F. H. (2009) · Nature · doi:10.1038/nature08248 · Cited by 814 · see citing works
Roles for retrotransposon insertions in human disease
Hancks, D. C., & Kazazian, H. H. (2016) · Mobile DNA · doi:10.1186/s13100-016-0065-9 · Cited by 670 · see citing works
Self-citationLINE-1 elements in structural variation and disease
Beck, C. R., Garcia-Perez, J. L., Badge, R. M., & Moran, J. V. (2011) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082509-141802 · Cited by 615 · see citing works
Dynamic interactions between transposable elements and their hosts
Levin, H. L., & Moran, J. V. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3030 · Cited by 621 · see citing works
Single-Neuron Sequencing Analysis of L1 Retrotransposition and Somatic Mutation in the Human Brain
Evrony, G. D., Cai, X., Lee, E., Hills, L. B., Elhosary, P. C., Lehmann, H. S., Parker, J. J., Atabay, K. D., Gilmore, E. C., Poduri, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.09.035 · Cited by 548 · see citing works
Restricting retrotransposons: a review
Goodier, J. L. (2016) · Mobile DNA · doi:10.1186/s13100-016-0070-z · Cited by 436 · see citing works
Mobile DNA in Health and Disease
Kazazian, H. H., & Moran, J. V. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510092 · Cited by 445 · see citing works
Self-citationCytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288 · see citing works
LINE-1 Evasion of Epigenetic Repression in Humans
Sanchez-Luque, F. J., Kempen, M.-J. H. C., Gerdes, P., Vargas-Landin, D. B., Richardson, S. R., Troskie, R.-L., Jesuadian, J. S., Cheetham, S. W., Carreira, P. E., Salvador-Palomeque, C., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.024 · Cited by 161 · see citing works
Jones, R. B., Garrison, K. E., Wong, J. C., Duan, E. H., Nixon, D. F., & Ostrowski, M. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001547 · Cited by 99 · see citing works
St. Laurent, G., Hammell, N., & McCaffrey, T. A. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.03.008 · Cited by 68 · see citing works
- Authors
- van den Hurk, J. A. J. M., Meij, I. C., del Carmen Seleme, M., Kano, H., Nikopoulos, K., Hoefsloot, L. H., Sistermans, E. A., de Wijs, I. J., Mukhopadhyay, A., Plomp, A. S., de Jong, P. T. V. M., Kazazian, H. H., & Cremers, F. P. M.
- Affiliations
- Max Delbrück Center (DE)
- University of Pennsylvania (US)
- Radboud University Medical Center (NL)
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Cremers, Frans P.M.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-04
- Volume
- 16
- Issue
- 13
- Pages
- 1587-1592
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2162146849
- Cited by
- 193
- References
- 33
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 12 · 2019: 9 · 2018: 17 · 2017: 20 · 2016: 22 · 2015: 7 · 2014: 10 · 2013: 16 · 2012: 8
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- L1 retrotransposition, LINE-1 retrotransposons, choroideremia, CHM gene, somatic mosaicism, germline mosaicism, human embryonic development
- MeSH terms
- Chromosomes, Human, Pair 6, Female, Heterozygote, Humans, Male, Models, Genetic, Mosaicism, Pedigree, Choroideremia, Germ-Line Mutation, Gene Expression Regulation, Developmental, Retroelements, Long Interspersed Nucleotide Elements, Chromosomes, Human, X, Embryonic Stem Cells
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