人类基因组核苷酸多态性位点核小体定位分析
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国家自然科学基金(30800209, 61073141)和江苏省自然科学基金(BK2010406)资助项目


Analysis of Nucleosome Positioning in The Vicinity of Sites of Nucleotide Polymorphism in Human Genome
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This work was supported by grants from The National Natural Science Foundation of China (30800209, 61073141) and The Jiangsu Natural Science Foundation (SBK201022749)

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    摘要:

    研究人类基因组核苷酸多态性位点周围核小体的定位,对于分析核苷酸的变异机制有重要意义.分析了人类基因组单核苷酸多态性(SNP)位点、简单插入位点、插入删除位点和删除位点的分布规律,以及这些位点周围的核小体定位特征.结果表明:转录起始位点下游的核苷酸多态性位点分布呈现约211 bp的周期特征,单核苷多态位点另有一个146 bp的周期;约211 bp的周期与转录起始位点下游核小体的分布周期204 bp非常接近,146 bp的周期恰是核小体核心DNA的长度.这些结果说明核小体与多态性位点的分布关系密切.进一步研究证实,单核苷酸多态性位点多分布于核心DNA上,且多位于核心DNA的两端,这使得单核苷酸多态性位点具有146 bp周期,而插入、插入删除、删除多态性位点多分布于核小体排开区域,间隔约为204 bp.转录起始位点下游核小体等间隔的规则分布使得多态性位点的分布也具有周期性.研究表明,相对于核小体,不同类型变异发生的位置不同,核小体定位在基因组多态性位点的形成过程中具有重要作用.

    Abstract:

    Studies of nucleosome positioning around the sites of nucleotide polymorphism are important for analysis of mechanism of genome variation. The distributions of sites single nucleotide polymorphism (SNP), simple insertion, insertion-deletion, and deletion are analyzed for human genome. Characteristics of nucleosomes in the vicinity of the polymorphism sites are also studied. The results indicated polymorphism sites downstream of transcription start sites (TSSs) occurs with an ~211 bp periodicities. For single nucleotide polymorphism, there is also a periodicity with 146 bp. The periodicity with ~211 bp is very close to the periodicity (204 bp) of nucleosome distribution downstream of TSS. The 146 bp periodicity is just the length of linker DNA sequence of a nucleosome. The results indicate that the distribution of polymorphism sites has an intimate relationship with nucleosome positioning. Further studies suggest that most of single nucleotide polymorphism sites are at two ends of core DNA, while sites of insertion, deletion, and insertion and deletion (in-del) tend to be in nucleosome-depleted region. The equally-spaced configuration of nucleosomes downstream of TSS causes the periodic distribution of polymorphism sites. The studies suggest genome variations occur in different regions relatively to nucleosomes, and nucleosome positioning has a role in forming nucleotide polymorphism.

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刘宏德,孙啸.人类基因组核苷酸多态性位点核小体定位分析[J].生物化学与生物物理进展,2011,38(5):427-432

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  • 收稿日期:2010-04-16
  • 最后修改日期:2010-11-05
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  • 在线发布日期: 2011-03-23
  • 出版日期: 2011-05-20