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首页> 外文期刊>Expert opinion on biological therapy >Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells
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Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells

机译：非结扎性胎儿非整倍体的非侵入性产前诊断，采用大规模平行依测序法进行，并证明母体血浆中无细胞的胎儿DNA来源于滋养细胞

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Blood plasma of pregnant women contains circulating cell-free fetal DNA (ccffDNA), originating from the placenta. The use of this DNA for non-invasive detection of fetal aneuploidies using massively parallel sequencing (MPS)-by-synthesis has been proven previously. Sequence performance may, however, depend on the MPS platform and therefore we have explored the possibility for multiplex MPS-by-ligation, using the Applied Biosystems SOLiD~(TM) 4 system. DNA isolated from plasma samples from 52 pregnant women, carrying normal or aneuploid fetuses, was sequenced in multiplex runs of 4, 8 or 16 samples simultaneously. The sequence reads were mapped to the human reference genome and quantified according to their genomic location. In case of a fetal aneuploidy, the number of reads of the aberrant chromosome is expected to be higher or lower than in normal reference samples. To statistically determine this, Z-scores per chromosome were calculated as described previously, with thresholds for aneuploidies set at > +3.0 and < -3.0 for chromosomal over- or underrepresentation, respectively. All samples from fetal aneuploidies yielded Z-scores outside the thresholds for the aberrant chromosomes, with no false negative or positive results. Full-blown fetal aneuploidies can thus be reliably detected in maternal plasma using a multiplex MPS-by-ligation approach. Furthermore, the results obtained with a sample from a pregnancy with 45,X in the cytotrophoblastic cell layer and 46,XX in the mesen-chymal core cells show that ccffDNA originates from the cytotrophoblastic cell layer. Discrepancies between the genetic constitution of this cell layer and the fetus itself are well known, and therefore, care should be taken when translating results to the fetus itself.
机译：孕妇的血浆中含有源自胎盘的循环性无细胞胎儿DNA（ccffDNA）。以前已经证明了使用这种DNA进行大规模合成测序（MPS）合成用于非侵入性检测胎儿非整倍性。但是，序列性能可能取决于MPS平台，因此，我们使用Applied Biosystems SOLiD〜TM 4系统探索了通过连接多重MPS的可能性。从52名携带正常或非整倍体胎儿的孕妇血浆样品中分离出的DNA在4、8或16个样品的同时运行中进行了测序。将序列读数定位到人类参考基因组，并根据其基因组位置进行定量。在胎儿非整倍性的情况下，异常染色体的阅读次数预计将比正常参考样品更高或更低。为了从统计学上确定这一点，如前所述计算每条染色体的Z得分，将非整倍性的阈值分别设置为> +3.0和<-3.0，以防止染色体过高或过低。胎儿非整倍性的所有样本产生的Z分数均超出异常染色体的阈值，没有假阴性或阳性结果。因此，使用多重MPS结扎方法可在母体血浆中可靠地检测出成熟的胎儿非整倍性。此外，从妊娠样品中获得的结果表明，滋养层细胞层中有45，X，间充质细胞核心细胞中有46，XX，其中ccffDNA来源于滋养层细胞。该细胞层的遗传结构与胎儿本身之间的差异是众所周知的，因此，在将结果翻译为胎儿本身时应格外小心。

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