TY - JOUR
T1 - Evidence consistent with human L1 retrotransposition in maternal meiosis I
AU - Brouha, Brook
AU - Meischl, Christof
AU - Ostertag, Eric
AU - De Boer, Martin
AU - Zhang, Yue
AU - Neijens, Herman
AU - Roos, Dirk
AU - Kazazian, Haig H.
N1 - Funding Information:
We thank Dr. P. M. van Hagen (Academic Hospital Dijkzigt, Rotterdam) for supplying patient material and relevant information. C.M. was supported by grant Me 1528/1-1 from the Deutsche Forschungsgemeinschaft and by a grant from the Stichting Fondsenwervingsacties Volksgezondheid (Foundation for Fund Raising in Public Health). H.H.K. was supported by a grant from the National Institutes of Health.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1086/341722
DO - 10.1086/341722
M3 - Article
C2 - 12094329
AN - SCOPUS:0036077271
SN - 0002-9297
VL - 71
SP - 327
EP - 336
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -