Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination.
Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination.
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2 型 NF1 缺失非常不寻常，因为不存在非等位基因同源重组热点并且明显偏好雌性有丝分裂重组。
DOI：
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发表时间：
2007
影响因子：
9.8
通讯作者：
H. Kehrer
中科院分区：
文献类型：
--
作者：
Katharina Steinmann;D. Cooper;L. Kluwe;N. Chuzhanova;C. Senger;E. Serra;C. Lázaro;M. Gilaberte;K. Wimmer;V. Mautner;H. Kehrer
大约5%的1型神经纤维瘤病（NF1）患者表现出包括NF1基因及其侧翼区域的总体缺失。常见的1.4 Mb（1型）缺失的断点位于低拷贝重复序列（NF1-REP）内，并聚集在非等位基因同源重组（NAHR）的3.4 kb热点内。在这里，我们提出了第一个全面的断点分析2型缺失，这是第二种类型的复发NF 1基因缺失。2型缺失跨越1.2 Mb，其特征在于位于SUZ12基因及其假基因内的断点，其紧密地侧翼NF1-REPs.Breakpoint分析的13个独立的2型缺失没有发现任何明显的热点NAHR。然而，多聚嘧啶/多聚嘌呤束和三链体形成序列的过度表达在断点区域中被注意到，这可能有助于NAHR。有趣的是，所有13个2型缺失的特点是体细胞镶嵌，这表明有丝分裂NAHR在NF 1基因区域内的位置偏好。事实上，染色体间减数分裂NAHR发生在NF1-REP之间，引起1型缺失，而有丝分裂期间NAHR似乎发生在染色体内SUZ12基因及其假基因之间，从而产生2型缺失。有丝分裂与减数分裂NAHR的优选位点之间的这种明确区别在由局部基因组结构诱导的任何其他基因组病症中是前所未有的。此外，13个嵌合体2型缺失中有12个在女性中发现。镶嵌2型缺失之间的显着女性优势与1型和/或非典型NF 1缺失的平等性别分布。虽然染色质结构的影响被强烈怀疑，没有性别特异性差异的SUZ12基因表现出的甲基化模式是明显的，可以解释较高的有丝分裂重组率在女性。
Approximately 5% of patients with neurofibromatosis type 1 (NF1) exhibit gross deletions that encompass the NF1 gene and its flanking regions. The breakpoints of the common 1.4-Mb (type 1) deletions are located within low-copy repeats (NF1-REPs) and cluster within a 3.4-kb hotspot of nonallelic homologous recombination (NAHR). Here, we present the first comprehensive breakpoint analysis of type 2 deletions, which are a second type of recurring NF1 gene deletion. Type 2 deletions span 1.2 Mb and are characterized by breakpoints located within the SUZ12 gene and its pseudogene, which closely flank the NF1-REPs. Breakpoint analysis of 13 independent type 2 deletions did not reveal any obvious hotspots of NAHR. However, an overrepresentation of polypyrimidine/polypurine tracts and triplex-forming sequences was noted in the breakpoint regions that could have facilitated NAHR. Intriguingly, all 13 type 2 deletions identified so far are characterized by somatic mosaicism, which indicates a positional preference for mitotic NAHR within the NF1 gene region. Indeed, whereas interchromosomal meiotic NAHR occurs between the NF1-REPs giving rise to type 1 deletions, NAHR during mitosis appears to occur intrachromosomally between the SUZ12 gene and its pseudogene, thereby generating type 2 deletions. Such a clear distinction between the preferred sites of mitotic versus meiotic NAHR is unprecedented in any other genomic disorder induced by the local genomic architecture. Additionally, 12 of the 13 mosaic type 2 deletions were found in females. The marked female preponderance among mosaic type 2 deletions contrasts with the equal sex distribution noted for type 1 and/or atypical NF1 deletions. Although an influence of chromatin structure was strongly suspected, no sex-specific differences in the methylation pattern exhibited by the SUZ12 gene were apparent that could explain the higher rate of mitotic recombination in females.
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影响因子：
9.8
作者：
Inoue, K;Osaka, H;Lupski, JR
通讯作者：
Lupski, JR
影响因子：
2.1
作者：
Olshen, AB;Venkatraman, ES;Wigler, M
通讯作者：
Wigler, M
影响因子：
4
作者：
R. Rizwana;P. Hahn
通讯作者：
R. Rizwana;P. Hahn
DOI：
10.1073/pnas.0405974101
发表时间：
2004-09-28
影响因子：
11.1
作者：
Bacolla, A;Jaworski, A;Wells, RD
通讯作者：
Wells, RD
影响因子：
7
作者：
Squazzo, Sharon L.;O'Geen, Henriette;Farnham, Peggy J.
通讯作者：
Farnham, Peggy J.