A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease
A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease
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DOI：
10.1038/sj.ejhg.5200523
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发表时间：
2000-09-01
影响因子：
5.2
通讯作者：
Roos, D
中科院分区：
文献类型：
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作者：
Meischl, C;de Boer, M;Roos, D
长穿插核素-1(Line-1)或L1元件是存在于基因组中的高拷贝数的DNA元件，具有主动逆转录转座的能力。在这里，我们提出了一个严重的慢性肉芽肿性疾病(CCD)患者，其原因是将L1序列插入到X-line基因CyBB的第5内含子中。由于内部重排，插入物在内含子中引入了新的剪接位点。这导致了高度异质性的剪接模式，将两个L1片段作为新的外显子引入到转录本中，并伴随着外显子编码序列的跳过。由于没有发现野生型cdna，这种机制可能与患者的表型有关。L1片段属于转录活性品系的Ta子集，它说明了一种新的机制，这些元件可以通过它来修改转录的基因编码序列。
Long interspersed nuclear element-1 (LINE-1) or L1 elements are DNA elements present in the genome in high copy number and capable of active retrotransposition. Here we present a patient with severe chronic granulomatous disease (CCD) caused by insertion of an L1 sequence into intron 5 of the X-lined gene CYBB. Due to internal rearrangements, the insert introduced new splice sites into the intron. This resulted in a highly heterogeneous splicing pattern with introduction of two L1 fragments as new exons into the transcripts and concomitant skipping of exonic coding sequence. Because no wild-type cDNA was found, this mechanism is probably responsible for the patient's phenotype. The L1 fragment, which belongs to the Ta subset of transcriptionally active LINEs, illustrates a new mechanism by which these elements can modify the transcribed coding sequence of genes.