van den Hurk José A J M, Meij Iwan C, Seleme Maria del Carmen, Kano Hiroki, Nikopoulos Konstantinos, Hoefsloot Lies H, Sistermans Erik A, de Wijs Ilse J, Mukhopadhyay Arijit, Plomp Astrid S, de Jong Paulus T V M, Kazazian Haig H, Cremers Frans P M
Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Hum Mol Genet. 2007 Jul 1;16(13):1587-92. doi: 10.1093/hmg/ddm108. Epub 2007 May 4.
L1 elements are autonomous retrotransposons that can cause hereditary diseases. We have previously identified a full-length L1 insertion in the CHM (choroideremia) gene of a patient with choroideremia, an X-linked progressive eye disease. Because this L1 element, designated L1(CHM), contains two 3'-transductions, we were able to delineate a retrotransposition path in which a precursor L1 on chromosome 10p15 or 18p11 retrotransposed to chromosome 6p21 and subsequently to the CHM gene on chromosome Xq21. A cell culture retrotransposition assay showed that L1(CHM) is one of the most active L1 elements in the human genome. Most importantly, analysis of genomic DNA from the CHM patient's relatives indicated somatic and germ-line mosaicism for the L1 insertion in his mother. These findings provide evidence that L1 retrotransposition can occur very early in human embryonic development.
L1元件是能够引发遗传性疾病的自主逆转录转座子。我们之前在一名患有脉络膜视网膜病变（一种X连锁进行性眼病）患者的CHM（脉络膜视网膜病变）基因中鉴定出一个全长L1插入。由于这个被命名为L1(CHM)的L1元件包含两个3'转导，我们得以描绘出一条逆转录转座路径，其中位于10号染色体p15或18号染色体p11上的一个前体L1逆转录转座至6号染色体p21，随后又转座至X染色体q21上的CHM基因。一项细胞培养逆转录转座试验表明，L1(CHM)是人类基因组中最活跃的L1元件之一。最重要的是，对该CHM患者亲属的基因组DNA分析表明，其母亲体内存在L1插入的体细胞和生殖系嵌合体。这些发现为L1逆转录转座可在人类胚胎发育极早期发生提供了证据。
