Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon.
Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon.
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DOI：
10.1002/humu.21663
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发表时间：
2012-02
期刊：
影响因子：
3.9
通讯作者：
Kazazian, Haig H., Jr.
中科院分区：
文献类型：
--
作者：
Solyom, Szilvia;Ewing, Adam D.;Hancks, Dustin C.;Takeshima, Yasuhiro;Awano, Hiroyuki;Matsuo, Masafumi;Kazazian, Haig H., Jr.
长插入元件-1（LINE-1）反转录转座子占人类基因组的17%，并且通过潜在的诱变“复制和粘贴”机制经由RNA中间体移动。最近，逆转录转座介导的插入一个新的转录被描述为一个新的原因遗传疾病，杜氏肌营养不良症，在日本男性。推测插入的序列来自于从chr. 11q22.3转录的单拷贝非编码RNA，其逆转录转座到肌营养不良蛋白基因中。在这里，我们证明了一个非参考全长LINE-1位于先证者和母体基因组中的chr。11q22.3，直接上游的序列，其拷贝插入到肌营养不良蛋白基因。该LINE-1在细胞培养试验中具有高活性。LINE-1插入通常与相邻基因组序列的3'转导相关。因此，诱变插入的可能解释是LINE-1介导的3'转导伴严重的5'截短。这是由“孤儿”3'转导引起的LINE-1诱导的人类疾病的第一个实例。
Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17% of the human genome, and move by a potentially mutagenic “copy and paste” mechanism via an RNA intermediate. Recently, the retrotransposition-mediated insertion of a new transcript was described as a novel cause of genetic disease, Duchenne muscular dystrophy, in a Japanese male. The inserted sequence was presumed to derive from a single-copy, non-coding RNA transcribed from chr. 11q22.3 that retrotransposed into the dystrophin gene. Here we demonstrate that a non-reference full-length LINE-1 is situated in the proband and maternal genome at chr. 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene. This LINE-1 is highly active in a cell culture assay. LINE-1 insertions are often associated with 3’ transduction of adjacent genomic sequences. Thus, the likely explanation for the mutagenic insertion is a LINE-1-mediated 3’ transduction with severe 5’ truncation. This is the first example of LINE-1-induced human disease caused by an “orphan” 3’ transduction.
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DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
30.8
作者：
Dewannieux, M;Esnault, C;Heidmann, T
通讯作者：
Heidmann, T
影响因子：
9.8
作者：
Brouha, B;Meischl, C;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
30.8
作者：
HOLMES, SE;DOMBROSKI, BA;KAZAZIAN, HH
通讯作者：
KAZAZIAN, HH
影响因子：
64.5
作者：
Beck CR;Collier P;Macfarlane C;Malig M;Kidd JM;Eichler EE;Badge RM;Moran JV
通讯作者：
Moran JV