Variation in array size, monomer composition and expression of the macrosatellite DXZ4.
Variation in array size, monomer composition and expression of the macrosatellite DXZ4.
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DOI：
10.1371/journal.pone.0018969
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发表时间：
2011-04-22
期刊：
影响因子：
3.7
通讯作者：
Chadwick BP
中科院分区：
文献类型：
--
作者：
Tremblay DC;Moseley S;Chadwick BP
大卫星是人类基因组中最具多态性的区域之一，尽管一些阵列与疾病易感性有关，但许多仍然没有被表征。本研究旨在探讨X连锁大卫星DXZ 4的多态性。从串联重复序列拷贝数变异、阵列不稳定性、单体序列多态性和阵列表达4个方面对DXZ 4基因进行了详细的研究。DXZ 4阵列含有12和100之间的3.0 kb重复单位，平均阵列含有57。通过限制性消化分析和延伸纤维FISH证实单体以不间断的串联阵列排列，因此DXZ 4包含36-288 kb的Xq 23。DXZ 4在三个家族中通过三代传播显示出高度的减数分裂不稳定性（8.3%），与其他宏卫星阵列一致，进一步突出了这些序列在人类基因组中的不稳定性。完整DXZ 4单体的亚克隆和测序鉴定了位于每个单体内的三个微卫星重复序列的许多单核苷酸多态性和等位基因。DXZ 4单体序列的成对比较显示，来自阵列的重复单元比来自不同阵列的重复单元彼此更相似。RNA荧光原位杂交显示DXZ 4表达在细胞系内和细胞系之间的显着变化。DXZ 4转录本可以检测到来自活性和非活性X染色体。DXZ 4的表达水平在雄性之间变化显著，但与阵列的大小无关，相同阵列的遗传也不会导致相似的表达水平。总的来说，这些研究为DXZ 4的多态性提供了相当多的见解，进一步突出了人类基因组中宏卫星的不稳定性和变异潜力。
Macrosatellites are some of the most polymorphic regions of the human genome, yet many remain uncharacterized despite the association of some arrays with disease susceptibility. This study sought to explore the polymorphic nature of the X-linked macrosatellite DXZ4. Four aspects of DXZ4 were explored in detail, including tandem repeat copy number variation, array instability, monomer sequence polymorphism and array expression. DXZ4 arrays contained between 12 and 100 3.0 kb repeat units with an average array containing 57. Monomers were confirmed to be arranged in uninterrupted tandem arrays by restriction digest analysis and extended fiber FISH, and therefore DXZ4 encompasses 36–288 kb of Xq23. Transmission of DXZ4 through three generations in three families displayed a high degree of meiotic instability (8.3%), consistent with other macrosatellite arrays, further highlighting the unstable nature of these sequences in the human genome. Subcloning and sequencing of complete DXZ4 monomers identified numerous single nucleotide polymorphisms and alleles for the three microsatellite repeats located within each monomer. Pairwise comparisons of DXZ4 monomer sequences revealed that repeat units from an array are more similar to one another than those originating from different arrays. RNA fluorescence in situ hybridization revealed significant variation in DXZ4 expression both within and between cell lines. DXZ4 transcripts could be detected originiating from both the active and inactive X chromosome. Expression levels of DXZ4 varied significantly between males, but did not relate to the size of the array, nor did inheritance of the same array result in similar expression levels. Collectively, these studies provide considerable insight into the polymorphic nature of DXZ4, further highlighting the instability and variation potential of macrosatellites in the human genome.
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影响因子：
3.7
作者：
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通讯作者：
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DOI：
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