Human L1 retrotransposition is associated with genetic instability in vivo
Human L1 retrotransposition is associated with genetic instability in vivo
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DOI：
10.1016/s0092-8674(02)00839-5
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发表时间：
2002-08-09
期刊：
影响因子：
64.5
通讯作者：
Boeke, JD
中科院分区：
文献类型：
--
作者：
Symer, DE;Connelly, C;Boeke, JD
数百万年来，逆转录转座子已经塑造了真核生物的基因组。为了分析人L1反转录转座的后果，我们开发了一种遗传系统来恢复体细胞中许多新的L1插入。回收了42个从头整合体，它们忠实地模仿了自灵长类辐射以来积累的L1的许多方面。它们的结构通过实验证明了L1反转录转座与各种形式的遗传不稳定性之间的关联。鉴定了许多L1元件倒位、额外核苷酸插入、外显子缺失、染色体倒位和侧翼序列共移动（称为5'转导）。在惊人数量的整合体中，供体和靶位点的3'端之间共享短的相同序列，这表明有助于解释Ll插入的结构的机制模型。
Retrotransposons have shaped eukaryotic genomes for millions of years. To analyze the consequences of human Ll retrotransposition, we developed a genetic system to recover many new L1 insertions in somatic cells. Forty-two de novo integrants were recovered that faithfully mimic many aspects of L1s that accumulated since the primate radiation. Their structures experimentally demonstrate an association between Ll retrotransposition and various forms of genetic instability. Numerous L1 element inversions, extra nucleotide insertions, exon deletions, a chromosomal inversion, and flanking sequence comobilization (called 5' transduction) were identified. In a striking number of integrants, short identical sequences were shared between the donor and the target site's 3' end, suggesting a mechanistic model that helps explain the structure of Ll insertions.