Population-specificity of human DNA methylation.
Population-specificity of human DNA methylation.
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DOI：
10.1186/gb-2012-13-2-r8
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发表时间：
2012-02-09
期刊：
影响因子：
12.3
通讯作者：
Kobor MS
中科院分区：
文献类型：
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作者：
Fraser HB;Lam LL;Neumann SM;Kobor MS
人类DNA甲基化的种族差异已被证明存在于许多CpG位点，但这些差异的全基因组模式和程度在很大程度上是未知的。此外，多态性DNA甲基化的遗传控制是否是种群特异性的还没有调查。在这里，我们测量了来自一个非洲人和一个欧洲人的180个细胞系中超过14000个基因的转录起始位点附近的DNA甲基化。我们在超过三分之一的基因中发现了群体特异性的DNA甲基化模式。此外，虽然超过一千个CpG位点的甲基化是可遗传的，但这些遗传性在人群之间也存在差异，这表明DNA甲基化的遗传控制存在广泛的差异。支持这一点，DNA甲基化的遗传作图表明，大多数群体特异性可以解释为群体之间等位基因频率的差异，并且群体之间的遗传关联几乎没有重叠。这些群体特异性遗传关联得到了数百个大脑样本中DNA甲基化模式的支持，表明它们在体内和组织中保持不变。这些结果表明，DNA甲基化是高度不同的人群之间，这种差异可能是由于在很大程度上的等位基因频率和复杂的上位性或基因×环境的相互作用的组合的差异。
Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are largely unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated. Here we measure DNA methylation near the transcription start sites of over 14, 000 genes in 180 cell lines derived from one African and one European population. We find population-specific patterns of DNA methylation at over a third of all genes. Furthermore, although the methylation at over a thousand CpG sites is heritable, these heritabilities also differ between populations, suggesting extensive divergence in the genetic control of DNA methylation. In support of this, genetic mapping of DNA methylation reveals that most of the population specificity can be explained by divergence in allele frequencies between populations, and that there is little overlap in genetic associations between populations. These population-specific genetic associations are supported by the patterns of DNA methylation in several hundred brain samples, suggesting that they hold in vivo and across tissues. These results suggest that DNA methylation is highly divergent between populations, and that this divergence may be due in large part to a combination of differences in allele frequencies and complex epistasis or gene × environment interactions.
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影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
3.7
作者：
Alberts, Rudi;Terpstra, Peter;Li, Yang;Breitling, Rainer;Nap, Jan-Peter;Jansen, Ritsert C.
通讯作者：
Jansen, Ritsert C.
影响因子：
9.8
作者：
Zhang, Dandan;Cheng, Lijun;Liu, Chunyu
通讯作者：
Liu, Chunyu
影响因子：
30.8
作者：
Spielman, Richard S.;Bastone, Laurel A.;Cheung, Vivian G.
通讯作者：
Cheung, Vivian G.
DOI：
10.1038/nrg2719
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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