Whole genome bisulfite sequencing of cell-free DNA and its cellular contributors uncovers placenta hypomethylated domains.
Whole genome bisulfite sequencing of cell-free DNA and its cellular contributors uncovers placenta hypomethylated domains.
复制标题
无细胞DNA及其细胞促进器的整个基因组硫酸氢盐测序可发现胎盘降低甲基化结构域。
DOI：
10.1186/s13059-015-0645-x
复制
发表时间：
2015-04-15
期刊：
影响因子：
12.3
通讯作者：
Ehrich M
中科院分区：
文献类型：
--
作者：
Jensen TJ;Kim SK;Zhu Z;Chin C;Gebhard C;Lu T;Deciu C;van den Boom D;Ehrich M
循环中的无细胞胎儿DNA使非侵入性产前胎儿非整倍体检测成为可能，而不会直接区分母体和胎儿DNA。通过专门丰富胎儿DNA的样本材料，检测可能会得到改进。DNA甲基化可能允许这样的DNA分离；然而，这取决于对循环中的无细胞DNA及其细胞贡献者的甲基组的了解。我们对一组不匹配的样本进行了全基因组亚硫酸氢盐测序，包括来自非怀孕和怀孕女性捐赠者的循环无细胞DNA，以及来自孕妇黄褐色外套和胎盘的基因组DNA。我们发现，较长片段中的CpG胞嘧啶更有可能甲基化。比较胎盘和非妊娠循环中无细胞DNA的甲基组，发现51,259个差异甲基化区域中的许多位于胎盘在数百万个连续碱基上表现出一致的低甲基化的区域。我们发现，这些胎盘低甲基化区域始终位于CpG和基因密度较低的区域。比较胎盘和非妊娠循环无细胞DNA时发现的差异甲基化区域在怀孕的循环无细胞DNA中重现，证实了在循环无细胞DNA混合物中检测差异甲基化的能力。我们在单碱基分辨率下生成了四种样本类型的甲基组图谱，确定了DNA甲基化和循环中无细胞DNA片段长度之间的联系，确定了样本组之间的差异甲基化区域，并发现了百万碱基大小的胎盘低甲基化区域的存在。本文的在线版本(doi：10.1186/s13059-0150645-x)包含补充材料，授权用户可以使用。
Circulating cell-free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the maternal and fetal DNA. Testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA; however, this depends on knowledge of the methylomes of circulating cell-free DNA and its cellular contributors. We perform whole genome bisulfite sequencing on a set of unmatched samples including circulating cell-free DNA from non-pregnant and pregnant female donors and genomic DNA from maternal buffy coat and placenta samples. We find CpG cytosines within longer fragments are more likely to be methylated. Comparison of the methylomes of placenta and non-pregnant circulating cell-free DNA reveal many of the 51,259 identified differentially methylated regions are located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases. We find these placenta hypomethylated domains are consistently located within regions exhibiting low CpG and gene density. Differentially methylated regions identified when comparing placenta to non-pregnant circulating cell-free DNA are recapitulated in pregnant circulating cell-free DNA, confirming the ability to detect differential methylation in circulating cell-free DNA mixtures. We generate methylome maps for four sample types at single-base resolution, identify a link between DNA methylation and fragment length in circulating cell-free DNA, identify differentially methylated regions between sample groups, and uncover the presence of megabase-size placenta hypomethylated domains. The online version of this article (doi:10.1186/s13059-015-0645-x) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
9.3
作者：
Chan, K. C. Allen;Ding, Chunming;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis
影响因子：
7
作者：
Hon, Gary C.;Hawkins, R. David;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
30.8
作者：
Futscher, BW;Oshiro, MM;Domann, FE
通讯作者：
Domann, FE
影响因子：
14.9
作者：
EHRLICH, M;GAMASOSA, MA;GEHRKE, C
通讯作者：
GEHRKE, C
影响因子：
9.3
作者：
Chim, Stephen S. C.;Jin, Shengnan;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis