Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood
Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood
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DOI：
10.1073/pnas.0808319105
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发表时间：
2008-10-21
影响因子：
11.1
通讯作者：
Quake, Stephen R.
中科院分区：
文献类型：
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作者：
Fan, H. Christina;Blumenfeld, Yair J.;Quake, Stephen R.
我们用高通量鸟枪测序技术直接对孕妇血浆中的无细胞DNA进行了测序，平均每个患者样本获得了500万个序列标签。这使我们能够测量非整倍体胎儿染色体的过多和过少。测序方法不依赖于多态，因此普遍适用于胎儿非整倍体的非侵入性检测。使用这种方法，我们成功地在18例正常和非整倍体妊娠的队列中确定了所有9例21三体(唐氏综合征)、2例18三体(Edward综合征)和1例13三体(Patau综合征)；三体早在14周就被检测到。直接测序也使我们能够研究无细胞血浆DNA的特征，我们发现有证据表明，这种DNA富含来自核小体的序列。
We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.