Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22.
Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22.
复制标题
高度相关的 1 型神经纤维瘤病 (NF1) 假基因在 2、14 和 22 号染色体上的传播机制。
DOI：
10.1038/sj.ejhg.5200434
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Hulsebos,TJ
中科院分区：
文献类型：
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作者：
Luijten,M;Wang,Y;Smith,BT;Westerveld,A;Smink,LJ;Dunham,I;Roe,BA;Hulsebos,TJ
1型神经纤维瘤病（NF1）是一种常见的遗传性疾病，涉及来自胚胎神经嵴的组织。除了在染色体臂17q上的功能基因外，nf1相关序列（假基因）还存在于包括2、12、14、15、18、21和22在内的许多染色体上。我们确定了22号染色体上NF1假基因的完整核苷酸序列。在这个假基因中只存在功能基因的中间部分，而不存在编码NF1蛋白功能上重要的gap相关结构域的外显子21-27a。除了14号染色体上两个已知的NF1假基因外，我们还鉴定了两个新的变异。通过系统发育树分析，我们发现位于第2、14和22号染色体上的NF1假基因具有亲缘关系。含有这些假基因之一的克隆与该亚群中的其他假基因交叉杂交，但未发现与功能性NF1基因或其他染色体上的NF1假基因的原位杂交。这表明它们的杂交特异性主要由假基因两侧的同源序列决定。通过对两翼区域的序列分析，这一概念得到了强有力的支持，同源性超过95%。我们假设在进化过程中，NF1假基因的这一部分最初是由功能性NF1基因的中间部分复制和转位到2号染色体而产生的。随后，一个更大的片段（包括侧翼序列）被复制，并在染色体14和22上产生了目前的NF1假基因拷贝。
Neurofibromatosis type 1 (NF1) is a frequent hereditary disorder that involves tissues derived from the embryonic neural crest. Besides the functional gene on chromosome arm 17q, NF1-related sequences (pseudogenes) are present on a number of chromosomes including 2, 12, 14, 15, 18, 21, and 22. We elucidated the complete nucleotide sequence of the NF1 pseudogene on chromosome 22. Only the middle part of the functional gene but not exons 21–27a, encoding the functionally important GAP-related domain of the NF1 protein, is presented in this pseudogene. In addition to the two known NF1 pseudogenes on chromosome 14 we identified two novel variants. A phylogenetic tree was constructed, from which we concluded that the NF1 pseudogenes on chromosomes 2, 14, and 22 are closely related to each other. Clones containing one of these pseudogenes cross-hybridised with the other pseudogenes in this subset, but did not reveal any in situ hybridisation with the functional NF1 gene or with NF1 pseudogenes on other chromosomes. This suggests that their hybridisation specificity is mainly determined by homologous sequences flanking the pseudogenes. Strong support for this concept was obtained by sequence analysis of the flanking regions, which revealed more than 95% homology. We hypothesise that during evolution this subset of NF1 pseudogenes initially arose by duplication and transposition of the middle part of the functional NF1 gene to chromosome 2. Subsequently, a much larger fragment, including flanking sequences, was duplicated and gave rise to the current NF1 pseudogene copies on chromosomes 14 and 22.