title: Evidence consistent with human L1 retrotransposition in maternal meiosis I.
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.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, 475 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Brook
authors.initials: B
authors.lastname: Brouha
authors.forename: Christof
authors.initials: C
authors.lastname: Meischl
authors.forename: Eric
authors.initials: E
authors.lastname: Ostertag
authors.forename: Martin
authors.initials: M
authors.lastname: de Boer
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Herman
authors.initials: H
authors.lastname: Neijens
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D005260:Female; D005434:Flow Cytometry; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D007223:Infant; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics; D008969:Molecular Sequence Data; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D009866:Oogenesis / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D019255:NADPH Oxidases