Evidence consistent with human L1 retrotransposition in maternal meiosis I - PubMed (original) (raw)
Case Reports
doi: 10.1086/341722. Epub 2002 Jul 1.
Affiliations
- PMID: 12094329
- PMCID: PMC379165
- DOI: 10.1086/341722
Case Reports
Evidence consistent with human L1 retrotransposition in maternal meiosis I
Brook Brouha et al. Am J Hum Genet. 2002 Aug.
Abstract
We have used a unique polymorphic 3' transduction to show that a human L1, or LINE-1 (long interspersed nucleotide element-1), retrotransposition event most likely occurred in the maternal primary oocyte during meiosis I. We characterized a truncated L1 retrotransposon with a 3' transduction that was inserted, in a Dutch male patient, into the X-linked gene CYBB, thereby causing chronic granulomatous disease. We used the unique flanking sequence to localize the precursor L1 locus, LRE3, to chromosome 2q24.1. In a cell culture assay, the retrotransposition frequency of LRE3 is greater than that for any other element that has been tested to date. The patient's mother had two LRE3 alleles that differed slightly in the 3'-flanking genomic DNA. The patient had a single LRE3 allele that was identical to one of the maternal alleles; however, the patient's insertion matched the maternal LRE3 allele that he did not inherit. Other data indicate that there is only a small chance that the father (unavailable for analysis) carries the precursor LRE3 allele. In addition, paternal origin of the insertion would have required that an LRE3 mRNA transcribed before meiosis II be carried separately from its precursor LRE3 allele in the fertilizing sperm. Since the mother carries a potential precursor allele and the insertion was on the patient's maternal X chromosome, it is highly likely that the insertion originated during maternal meiosis I.
Figures
Figure 1
Insertion analyses. _A, CYBB-_specific Southern blot with _Eco_RI-digested DNA—from an unrelated control individual, the patient's mother, and the patient—demonstrating the shift, in the patient's sample, of the exon 4–containing fragment. The sizes of the wild-type bands are given; the arrow (←) indicates the aberrant band. The probe was constructed with coding cDNA of CYBB as template. B, Expand Long Template PCR of exon 4, in the patient, the patient’s mother, and an unrelated control. The arrows (→) indicate markers in the ladder.
Figure 2
Insertion sequence analyses. A, Schematic representation of the CYBB insertion. PT = important sequence of a PCR product from the patient’s exon 4. _B, CYBB-_insertion sequence alignments. CYBB = GenBank sequence at the point of insertion, into exon 4, of CYBB; PT = sequence of a PCR product from the patient’s CYBB exon 4 (which includes the disease-causing insertion); LRE3 = sequence of a PCR product from the patient’s chromosome 2q24.1; L1RP = GenBank sequence of the most active element known (the nucleotide number of the adjacent base is given in parentheses). A possible 2-bp TSD in the disease-causing insertion is underlined; differences between sequences are shaded; leader dots indicate sequence that is consistent with the L1RP sequence.
Figure 3
Expand Long Template PCR with flanking primers, demonstrating the presence or absence of LRE3 in the patient's mother, in the patient, and in an unrelated heterozygote. All bands were sequenced, to confirm findings.
Figure 4
LRE3 sequence analyses. A, Schematic representation of the LRE3 insertion into chromosome 2q24.1. LRE3 = important sequence from LRE3. Potential TSDs are underlined; asterisks (*) are placed at locations where differences exist between LRE3 and L1RP. The larger asterisk indicates an amino acid change. B, LRE3 sequence alignments. CHR2 = GenBank sequence's “empty site” at the LRE3 locus; LRE3 = sequence of a PCR product from both the patient’s chromosome 2q24.1 and the patient's mother’s chromosome 2q24.1; L1RP = GenBank sequence of the most active element known (the nucleotide number of the adjacent base is given in parentheses). A possible 28-bp TSD of LRE3 is underlined; nucleotide differences are shaded; leader dots indicate sequence that is consistent with the L1RP sequence.
Figure 5
Example of flow-cytometry results. A live/dead gate was set by use of forward and sideward scatter of cells, and ∼10,000 live cells were assayed for fluorescence. Cells within the M1 marker were counted as positive. The M1 marker was zeroed using a single JM111 clone (L1RP, with two disabling ORF1 point mutations) and a single L1RP clone (not shown) that lacked the 3,832-bp _Afl_II fragment. Both negative controls were assayed in triplicate; one L1RP clone was assayed in triplicate, as a positive control; two LRE3 clones, one derived from maternal genomic DNA and another derived from patient genomic DNA, were assayed in triplicate. Numbers give the average number, over three assays, of positive cells for each clone ± 1 SD.
Figure 6
Assay and gel analyses. A, Schematic representation of the polymorphism assay that was used to determine the absence or presence of an element. B, Sample gel, showing results from 20 individuals of diverse ethnic backgrounds.
Similar articles
- Primary immunodeficiency caused by an exonized retroposed gene copy inserted in the CYBB gene.
de Boer M, van Leeuwen K, Geissler J, Weemaes CM, van den Berg TK, Kuijpers TW, Warris A, Roos D. de Boer M, et al. Hum Mutat. 2014 Apr;35(4):486-96. doi: 10.1002/humu.22519. Epub 2014 Feb 24. Hum Mutat. 2014. PMID: 24478191 - A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease.
Meischl C, Boer M, Ahlin A, Roos D. Meischl C, et al. Eur J Hum Genet. 2000 Sep;8(9):697-703. doi: 10.1038/sj.ejhg.5200523. Eur J Hum Genet. 2000. PMID: 10980575 - A second case of somatic triple mosaicism in the CYBB gene causing chronic granulomatous disease.
Noack D, Heyworth PG, Kyono W, Cross AR. Noack D, et al. Hum Genet. 2001 Aug;109(2):234-8. doi: 10.1007/s004390100551. Hum Genet. 2001. PMID: 11511930 - L1 elements, processed pseudogenes and retrogenes in mammalian genomes.
Ding W, Lin L, Chen B, Dai J. Ding W, et al. IUBMB Life. 2006 Dec;58(12):677-85. doi: 10.1080/15216540601034856. IUBMB Life. 2006. PMID: 17424906 Review. - L1 retrotransposons and somatic mosaicism in the brain.
Richardson SR, Morell S, Faulkner GJ. Richardson SR, et al. Annu Rev Genet. 2014;48:1-27. doi: 10.1146/annurev-genet-120213-092412. Epub 2014 Jul 14. Annu Rev Genet. 2014. PMID: 25036377 Review.
Cited by
- LINE-1 retrotransposons contribute to mouse PV interneuron development.
Bodea GO, Botto JM, Ferreiro ME, Sanchez-Luque FJ, de Los Rios Barreda J, Rasmussen J, Rahman MA, Fenlon LR, Jansz N, Gubert C, Gerdes P, Bodea LG, Ajjikuttira P, Da Costa Guevara DJ, Cumner L, Bell CC, Kozulin P, Billon V, Morell S, Kempen MHC, Love CJ, Saha K, Palmer LM, Ewing AD, Jhaveri DJ, Richardson SR, Hannan AJ, Faulkner GJ. Bodea GO, et al. Nat Neurosci. 2024 Jul;27(7):1274-1284. doi: 10.1038/s41593-024-01650-2. Epub 2024 May 21. Nat Neurosci. 2024. PMID: 38773348 Free PMC article. - LINE-1 Retrotransposition Assays in Embryonic Stem Cells.
Garcia-Cañadas M, Sanchez-Luque FJ, Sanchez L, Rojas J, Garcia Perez JL. Garcia-Cañadas M, et al. Methods Mol Biol. 2023;2607:257-309. doi: 10.1007/978-1-0716-2883-6_13. Methods Mol Biol. 2023. PMID: 36449167 - Somatic retrotransposition in the developing rhesus macaque brain.
Billon V, Sanchez-Luque FJ, Rasmussen J, Bodea GO, Gerhardt DJ, Gerdes P, Cheetham SW, Schauer SN, Ajjikuttira P, Meyer TJ, Layman CE, Nevonen KA, Jansz N, Garcia-Perez JL, Richardson SR, Ewing AD, Carbone L, Faulkner GJ. Billon V, et al. Genome Res. 2022 Jul;32(7):1298-1314. doi: 10.1101/gr.276451.121. Epub 2022 Jun 21. Genome Res. 2022. PMID: 35728967 Free PMC article. - Cytoplasmic DNA: sources, sensing, and role in aging and disease.
Miller KN, Victorelli SG, Salmonowicz H, Dasgupta N, Liu T, Passos JF, Adams PD. Miller KN, et al. Cell. 2021 Oct 28;184(22):5506-5526. doi: 10.1016/j.cell.2021.09.034. Cell. 2021. PMID: 34715021 Free PMC article. Review. - Control of LINE-1 Expression Maintains Genome Integrity in Germline and Early Embryo Development.
Kohlrausch FB, Berteli TS, Wang F, Navarro PA, Keefe DL. Kohlrausch FB, et al. Reprod Sci. 2022 Feb;29(2):328-340. doi: 10.1007/s43032-021-00461-1. Epub 2021 Jan 22. Reprod Sci. 2022. PMID: 33481218 Review.
References
Electronic-Database Information
- GenBank, http://www.ncbi.nlm.nih.gov/Genbank/ (for Homo sapiens BAC clone RP11-81F8 [accession number AC067958])
- Human Gene Mutation Database, The, http://archive.uwcm.ac.uk/uwcm/mg/search/120513.html (for CYBB mutations)
- Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for CGD [MIM 306400])
References
- Boissinot S, Chevret P, Furano AV (2000) L1 (LINE-1) retrotransposon evolution and amplification in recent human history. Mol Biol Evol 17:915–928 - PubMed
- Browning VL, Chaudhry SS, Planchart A, Dixon MJ, Schimenti JC (2001) Mutations of the mouse Twist and sy (fibrillin 2) genes induced by chemical mutagenesis of ES cells. Genomics 73:291–298 - PubMed
- Cost GJ, Boeke JD (1998) Targeting of human retrotransposon integration is directed by the specificity of the L1 endonuclease for regions of unusual DNA structure. Biochemistry 37:18081–18093 - PubMed
- Dombroski B, Mathias S, Nanthakumar E, Scott A, Kazazian HH Jr (1991) Isolation of an active human transposable element. Science 254:1805–1808 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous