We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung-transplant recipients, we showed that, at 72 hours after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donorspecific alleles and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumorspecific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring and cancer screening.

中文翻译：

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遗传表观遗传组织定位技术在血浆DNA检测中的应用

我们开发了遗传表观遗传组织定位图（GETMap），通过比较血浆甲基化谱图与相关组织，从而确定携带基因组基因组中不存在的遗传变异的血浆DNA的组织组成。我们通过证明在孕妇中，携带胎儿特异性等位基因的循环DNA完全是胎盘来源来验证这种方法的。在肺移植受者中，我们表明，在移植后72小时，肺对携带供体特异性等位基因的血浆DNA的贡献仅为17％，而造血细胞的贡献为78％。在肝细胞癌患者中，肝脏被认为是携带肿瘤特异性突变的血浆DNA的主要来源。在患有淋巴瘤的孕妇中，准确地显示出携带癌症突变和胎儿特异性等位基因的血浆DNA分子分别来自淋巴细胞和胎盘。携带遗传变异的血浆DNA的组织来源分析可能对无创产前检测，移植监测和癌症筛查有用。