Dynamics and processes of copy number instability in human γ-globin genes
Dynamics and processes of copy number instability in human γ-globin genes
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人类γ珠蛋白基因拷贝数不稳定的动态和过程
DOI：
10.1073/pnas.1003634107
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
A. Jeffreys
中科院分区：
文献类型：
--
作者：
R. Neumann;Victoria E Lawson;A. Jeffreys
人类基因组的拷贝数变异是普遍存在的，但对DNA重排的动力学知之甚少。因此，我们使用重复的γ-珠蛋白基因作为一个简单的系统来探索从头拷贝数的变化。在生殖系和体细胞DNA中都可以看到改变基因数量的重排，主要是由同源序列之间的不平等姐妹染色单体交换引起的，经常性的镶嵌重排表明，许多（如果不是全部）精子中的这些事件发生在减数分裂之前。不平等的交换频率显然主要由重复基因共享的序列同一性程度控制，导致单倍型之间拷贝数不稳定性的实质性变化。此外，还检测到由不涉及同源重组的机制产生的更复杂的重排，并且在某些情况下显示染色体之间的DNA转移，但很少见。在γ-珠蛋白DNA分子中也观察到序列变化，强有力的证据表明有些是真正的从头碱基取代。它们存在于精子中的频率远远高于目前对生殖系突变率的估计，这引发了关于男性生殖系中碱基突变动态的有趣问题。
Copy number variation in the human genome is prevalent but relatively little is known about the dynamics of DNA rearrangement. We therefore used the duplicated γ-globin genes as a simple system to explore de novo copy number changes. Rearrangements that changed gene number were seen in both germline and somatic DNA, and mainly arose by unequal sister chromatid exchange between homologous sequences, with evidence from recurrent mosaic rearrangements that many, if not all, of these events in sperm arise before meiosis. Unequal exchange frequencies are apparently controlled primarily by the degree of sequence identity shared by the duplicate genes, leading to substantial variation between haplotypes in copy number instability. Additional, more complex rearrangements generated by mechanisms not involving homologous recombination, and in some cases showing DNA transfer between chromosomes, were also detected but were rare. Sequence changes were also seen in γ-globin DNA molecules, with strong evidence that some were genuine de novo base substitutions. They were present in sperm at a frequency far higher than predicted from current estimates of germline mutation rates, raising interesting questions about base mutation dynamics in the male germline.
错配修复机制在调节酵母分歧序列之间有丝分裂和减数分裂重组中的作用。
影响因子：
3.3
作者：
Chen,W;Jinks-Robertson,S
通讯作者：
Jinks-Robertson,S
基因转换及其与同源染色体配对的关系。
DOI：
10.1098/rstb.1986.0008
发表时间：
1986
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Smithies,O;Powers,PA
通讯作者：
Powers,PA
影响因子：
56.9
作者：
BORTS, RH;HABER, JE
通讯作者：
HABER, JE