Gene conversion causing human inherited disease: evidence for involvement of non-B-DNA-forming sequences and recombination-promoting motifs in DNA breakage and repair.
Gene conversion causing human inherited disease: evidence for involvement of non-B-DNA-forming sequences and recombination-promoting motifs in DNA breakage and repair.
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DOI：
10.1002/humu.21020
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发表时间：
2009-08
期刊：
影响因子：
3.9
通讯作者：
Cooper, David N.
中科院分区：
文献类型：
--
作者：
Chuzhanova, Nadia;Chen, Jian-Min;Bacolla, Albino;Patrinos, George P.;Ferec, Claude;Wells, Robert D.;Cooper, David N.
已经报道了多种DNA序列基序，包括反向重复序列、小卫星和χ重组热点，与引起遗传性疾病的人类基因中的基因转换相关。然而，没有进行系统的基于统计学的分析来正式确定这些观察结果。我们对遗传性疾病背景下报道的19个不同基因中的27个非重叠基因转换事件所涉及的DNA序列片段进行了计算机模拟分析。我们发现，基因转换事件往往发生在（C+G）-和CpG-丰富的区域和序列的潜力，形成非B-DNA结构，这可能涉及到的双链断裂，反过来可以促进基因转换的产生，发生不成比例的最大转换道和/或短侧翼区。还发现最大转化片段富集（p<0.01）截短形式的X元件（TGGTGG基序）、免疫球蛋白重链类别转换重复、translin靶位点和几个新的基序，包括（或重叠）经典减数分裂重组热点CCTCCCCT。最后，基因转换倾向于发生在有可能折叠成稳定发夹构象的基因组区域。这些发现支持了这样的概念，即重组诱导基序与替代DNA构象相关联，可以促进人类基因组中的重组。
A variety of DNA sequence motifs including inverted repeats, minisatellites, and the χ recombination hotspot, have been reported in association with gene conversion in human genes causing inherited disease. However, no methodical statistically-based analysis has been performed to formalize these observations. We have performed an in silico analysis of the DNA sequence tracts involved in 27 non-overlapping gene conversion events in 19 different genes reported in the context of inherited disease. We found that gene conversion events tend to occur within (C+G)- and CpG-rich regions and that sequences with the potential to form non-B-DNA structures, and which may be involved in the generation of double-strand breaks that could in turn serve to promote gene conversion, occur disproportionately within maximal converted tracts and/or short flanking regions. Maximal converted tracts were also found to be enriched (p<0.01) in a truncated version of the χ-element (a TGGTGG motif), immunoglobulin heavy chain class switch repeats, translin target sites and several novel motifs including (or overlapping) the classical meiotic recombination hotspot, CCTCCCCT. Finally, gene conversions tend to occur in genomic regions that have the potential to fold into stable hairpin conformations. These findings support the concept that recombination-inducing motifs, in association with alternative DNA conformations, can promote recombination in the human genome.
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CpG岛密度及其与哺乳动物基因组中基因组特征的相关性。
影响因子：
12.3
作者：
Han L;Su B;Li WH;Zhao Z
通讯作者：
Zhao Z
影响因子：
64.8
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通讯作者：
Skol, Andrew
影响因子：
15.9
作者：
GLOBERMAN, H;AMOR, M;WHITE, PC
通讯作者：
WHITE, PC
影响因子：
64.5
作者：
FLANAGAN, JG;LEFRANC, MP;RABBITTS, TH
通讯作者：
RABBITTS, TH
影响因子：
9.8
作者：
Cullen, M;Perfetto, SP;Carrington, M
通讯作者：
Carrington, M