Régnier V, Meddeb M, Lecointre G, Richard F, Duverger A, Nguyen V C, Dutrillaux B, Bernheim A, Danglot G
Cytogénétique et Génétique Oncologiques, CNRS URA 1967, Institut Gustave Roussy, Villejuif, France.
Hum Mol Genet. 1997 Jan;6(1):9-16. doi: 10.1093/hmg/6.1.9.
Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha-satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.
1型神经纤维瘤病（NF1）基因编码一种GTP酶激活蛋白家族成员，被认为是一种肿瘤抑制基因。其在人类中的极高新发突变率促使我们研究该基因的一个特定特征：存在众多与NF1相关的序列。根据我们的研究结果，人类基因组至少包含11个与NF1相关的序列，其中9个分散在7条不同染色体的着丝粒序列附近。这些与NF1相关的序列，其长度因位点而异，是NF1基因的未加工拷贝，并带有大量突变。对六个最大序列的系统发育分析表明，它们均源自一个共同祖先，该祖先大约出现在2200万至3300万年前，随后在类人猿进化过程中多次重复。最近的一次重复和染色体间转座发生在过去一百万年中，这表明该过程可能仍在进行。α卫星DNA和与NF1相关序列的进化之间有趣的相似性表明，这些NF1部分拷贝的产生和着丝粒周围扩散涉及一种共同的遗传机制。
