Abstract：
Deep sequencing by NGS of targeted amplicons can identify rare genetic variants in a pool of DNA where the vast majority of genomic DNA does not contain the variant. This approach can be used to detect a previously described paternally inherited, fetal variant in cell-free DNA (cfDNA) in maternal plasma. This is useful in cases where risk for the fetus is contingent upon inheritance of a paternal variant that the woman does not have. Both pathogenic and non-pathogenic variants that the woman does not have can be detected. In cases of compound heterozygosity, presence of the paternal pathogenic variant also requires detection of the maternal variant for risk assessment, which requires a chorion villus biopsy.We have used this approach to focus on detection of fetal blood groups in cases of presence of maternal alloantibodies against blood group antigens in pregnancy, to predict whether the fetus has inherited a blood group antigen that is targeted by the alloantibodies. In cases of maternal alloantibodies against blood group antigens, the fetus is at risk of hemolytic disease of the fetus and newborn (HDFN). With a known specificity of the maternal antibodies and if the fetal blood group can be determined in the pregnancy, then it can be ascertained if the fetus is at risk of HDFN and rational pregnancy care can be instituted. A noninvasive procedure avoids risks for the fetus. We have reported a procedure based on NGS analysis of PCR amplified cfDNA from maternal plasma. Some fetuses may die as early as week 18. We use this approach to predict fetal K, k, RhC, Rhc, RhE, and ABO blood groups in cases with a risk of HDFN due to the corresponding maternally produced antibodies.The NGS-based analysis can predict the presence or absence of incompatible antigens on the fetal RBCs.In this chapter, a noninvasive method for predicting some fetal blood groups early in pregnancy is described. There is a clinical need for such assays, and they may be a useful tool for management of pregnancies complicated by these alloantibodies within the field of precision medicine.
摘要：
通过NGS对靶向扩增子的深度测序可以鉴定DNA池中的罕见遗传变体,其中绝大多数基因组DNA不包含变体。这种方法可用于检测先前描述的父系遗传，母体血浆中无细胞DNA（cfDNA）的胎儿变异。这在胎儿的风险取决于女性没有的父亲变异的遗传的情况下是有用的。可以检测到女性没有的致病性和非致病性变体。在复合杂合性的情况下，父系致病变异的存在还需要检测母系变异以进行风险评估，需要做绒毛膜绒毛活检.我们已经使用这种方法来专注于在怀孕期间存在针对血型抗原的母体同种抗体的情况下检测胎儿血型。预测胎儿是否遗传了同种抗体靶向的血型抗原。在针对血型抗原的母体同种抗体的情况下，胎儿有胎儿和新生儿溶血病（HDFN）的风险。具有已知的母体抗体特异性，并且如果可以在怀孕期间确定胎儿血型，然后可以确定胎儿是否有HDFN的风险，并可以建立合理的怀孕护理。非侵入性手术避免了胎儿的风险。我们已经报道了基于从母体血浆中PCR扩增的cfDNA的NGS分析的程序。有些胎儿可能早在第18周死亡。我们用这种方法来预测胎儿K，k,RhC,Rhc,RHE,和ABO血型在有HDFN风险的情况下，由于相应的母体产生的抗体。基于NGS的分析可以预测胎儿RBC上不相容抗原的存在或不存在。在这一章中,描述了一种在妊娠早期预测某些胎儿血型的非侵入性方法。临床上需要这样的检测方法，他们可能是一个有用的工具来管理妊娠复杂的这些同种抗体领域的精准医学。
