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本文引用的文献

1
Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.拷贝数变异的表型后果:来自 Smith-Magenis 和 Potocki-Lupski 综合征小鼠模型的见解。
PLoS Biol. 2010 Nov 23;8(11):e1000543. doi: 10.1371/journal.pbio.1000543.
2
The effect of translocation-induced nuclear reorganization on gene expression.易位诱导的核重排对基因表达的影响。
Genome Res. 2010 May;20(5):554-64. doi: 10.1101/gr.103622.109. Epub 2010 Mar 8.
3
The clinical context of copy number variation in the human genome.人类基因组中拷贝数变异的临床背景。
Expert Rev Mol Med. 2010 Mar 9;12:e8. doi: 10.1017/S1462399410001390.
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Evolution in health and medicine Sackler colloquium: Genomic disorders: a window into human gene and genome evolution.健康与医学领域的演变:萨克勒研讨会——基因组疾病:洞察人类基因与基因组进化的窗口
Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1(Suppl 1):1765-71. doi: 10.1073/pnas.0906222107. Epub 2010 Jan 13.
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Gene copy number variation and common human disease.基因拷贝数变异与常见人类疾病。
Clin Genet. 2010 Mar;77(3):201-13. doi: 10.1111/j.1399-0004.2009.01342.x. Epub 2009 Dec 10.
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Origins and functional impact of copy number variation in the human genome.人类基因组中拷贝数变异的起源和功能影响。
Nature. 2010 Apr 1;464(7289):704-12. doi: 10.1038/nature08516. Epub 2009 Oct 7.
7
Copy number variation in human health, disease, and evolution.人类健康、疾病与进化中的拷贝数变异
Annu Rev Genomics Hum Genet. 2009;10:451-81. doi: 10.1146/annurev.genom.9.081307.164217.
8
Copy number variation influences gene expression and metabolic traits in mice.拷贝数变异影响小鼠的基因表达和代谢特征。
Hum Mol Genet. 2009 Nov 1;18(21):4118-29. doi: 10.1093/hmg/ddp360. Epub 2009 Jul 31.
9
Copy number variants, diseases and gene expression.拷贝数变异、疾病与基因表达。
Hum Mol Genet. 2009 Apr 15;18(R1):R1-8. doi: 10.1093/hmg/ddp011.
10
Segmental copy number variation shapes tissue transcriptomes.节段性拷贝数变异塑造组织转录组。
Nat Genet. 2009 Apr;41(4):424-9. doi: 10.1038/ng.345. Epub 2009 Mar 8.

拷贝数变异会改变表达的时程。

Copy number variation modifies expression time courses.

机构信息

Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.

出版信息

Genome Res. 2011 Jan;21(1):106-13. doi: 10.1101/gr.112748.110. Epub 2010 Nov 17.

DOI:10.1101/gr.112748.110
PMID:21084671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3012917/
Abstract

A preliminary understanding into the phenotypic effect of DNA segment copy number variation (CNV) is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes that map within them. They were also shown to modify the expression of genes located on their flanks and sometimes those at a great distance from their boundary. Here we demonstrate, by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained through life. However, we find that some brain-expressed genes mapping within CNVs appear to be under compensatory loops only at specific time points, indicating that the effect of CNVs on these genes is modulated during development. Notably, we also observe that CNV genes are significantly enriched within transcripts that show variable time courses of expression between strains. Thus, modifying the copy number of a gene may potentially alter not only its expression level, but also the timing of its expression.

摘要

对 DNA 片段拷贝数变异 (CNV) 的表型效应的初步了解正在出现。这些重排以某种剂量依赖的方式影响映射在它们内部的基因的表达。它们还被证明可以修饰位于它们侧翼的基因以及有时位于它们边界远处的基因的表达。在这里,我们通过在多个生命阶段监测这些效应来证明,这些表达控制在整个小鼠发育过程中都是有效的。同样,我们观察到 CNV 基因的更具体的空间表达模式在整个生命周期中都得到维持。然而,我们发现,一些映射在 CNV 内的大脑表达基因似乎仅在特定时间点受到补偿回路的控制,这表明 CNV 对这些基因的影响在发育过程中是被调节的。值得注意的是,我们还观察到 CNV 基因在显示不同品系之间表达时间变化的转录本中显著富集。因此,改变一个基因的拷贝数可能不仅会改变其表达水平,还会改变其表达的时间。