Evidence consistent with human L1 retrotransposition in maternal meiosis I
Evidence consistent with human L1 retrotransposition in maternal meiosis I
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DOI：
10.1086/341722
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发表时间：
2002-08-01
影响因子：
9.8
通讯作者：
Kazazian, HH
中科院分区：
文献类型：
--
作者：
Brouha, B;Meischl, C;Kazazian, HH
我们利用一种独特的多态性3'转导表明，一个人类L1（即长散在核元件 - 1，LINE - 1）的逆转录转座事件很可能发生在减数分裂I期间的母源初级卵母细胞中。我们对一个带有3'转导的截短L1逆转录转座子进行了特征分析，它插入到一名荷兰男性患者的X连锁基因CYBB中，从而导致慢性肉芽肿病。我们利用独特的侧翼序列将前体L1基因座LRE3定位到染色体2q24.1。在细胞培养实验中，LRE3的逆转录转座频率高于迄今为止测试过的任何其他元件。患者的母亲有两个LRE3等位基因，其3'侧翼基因组DNA略有不同。患者有一个单一的LRE3等位基因，与母亲的其中一个等位基因相同；然而，患者的插入片段与他未遗传到的母亲的LRE3等位基因匹配。其他数据表明，父亲（无法进行分析）携带前体LRE3等位基因的可能性很小。此外，如果插入片段是父源的，就需要在减数分裂II之前转录的LRE3 mRNA在受精精子中与其前体LRE3等位基因分开携带。由于母亲携带一个潜在的前体等位基因，并且插入发生在患者的母源X染色体上，所以插入很可能起源于母源减数分裂I期间。
We have used a unique polymorphic 3' transduction to show that a human L1, or LINE-1 ((l) under bar ong (i) under bar nterspersed (n) under bar ucleotide (e) under bar lement-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.