Feasibility for non-invasive prenatal fetal blood group and platelet genotyping by massively parallel sequencing: A single test system for multiple atypical red cell, platelet and quality control markers,British Journal of Haematology

当前位置： X-MOL 学术 › Br. J. Haematol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Feasibility for non-invasive prenatal fetal blood group and platelet genotyping by massively parallel sequencing: A single test system for multiple atypical red cell, platelet and quality control markers
British Journal of Haematology ( IF 5.1 ) Pub Date : 2023-11-20 , DOI: 10.1111/bjh.19197
Eunike C McGowan ₁ , Helen O'Brien _{1,

2} , Mia E Sarri ₁ , Genghis H Lopez _{1,

3} , James J Daly ₄ , Robert L Flower _{1,

5} , Glenn J Gardener ₆ , Catherine A Hyland _{1,

5}

Affiliation

Non-invasive prenatal tests (NIPT) to predict fetal red cell or platelet antigen status for alloimmunised women are provided for select antigens. This study reports on massively parallel sequencing (MPS) using a red cell and platelet probe panel targeting multiple nucleotide variants, plus individual identification single nucleotide polymorphisms (IISNPs). Maternal blood samples were provided from 33 alloimmunised cases, including seven with two red cell antibodies. Cell-free and genomic DNA was sequenced using targeted MPS and bioinformatically analysed using low-frequency variant detection. The resulting maternal genomic DNA allele frequency was subtracted from the cell-free DNA counterpart. Outcomes were matched against validated phenotyping/genotyping methods, where available. A 2.5% subtractive allele frequency threshold was set after comparing MPS predictions for K, RhC/c, RhE/e and Fy^a/Fy^b against expected outcomes. This threshold was used for subsequent predictions, including HPA-15a, Jk^a/Jk^b, Kp^a/Kp^b and Lu^a. MPS outcomes were 97.2% concordant with validated methods; one RhC case was discordantly negative and lacked IISNPs. IISNPs were informative for 30/33 cases as controls. NIPT MPS is feasible for fetal blood group genotyping and covers multiple blood groups and control targets in a single test. Noting caution for the Rh system, this has the potential to provide a personalised service for alloimmunised women.

中文翻译：

通过大规模并行测序进行非侵入性产前胎儿血型和血小板基因分型的可行性：用于多种非典型红细胞、血小板和质量控制标记物的单一测试系统

针对特定抗原，提供非侵入性产前检测 (NIPT)，用于预测同种免疫女性的胎儿红细胞或血小板抗原状态。这项研究报告了使用红细胞和血小板探针组针对多个核苷酸变异以及个体识别单核苷酸多态性 (IISNP) 的大规模并行测序 (MPS)。母体血液样本来自 33 个同种免疫病例，其中 7 个病例带有两种红细胞抗体。使用靶向 MPS 对游离细胞和基因组 DNA 进行测序，并使用低频变异检测进行生物信息分析。从无细胞 DNA 对应物中减去所得母体基因组 DNA 等位基因频率。结果与经过验证的表型/基因分型方法（如果可用）进行匹配。将 K、RhC/c、RhE/e 和 Fy ^a /Fy ^b的 MPS 预测与预期结果进行比较后，设置了 2.5% 扣除等位基因频率阈值。该阈值用于后续预测，包括 HPA-15a、Jk ^a /Jk ^b 、Kp ^a /Kp ^b和 Lu ^a 。 MPS 结果与验证方法的一致性为 97.2%； 1 例 RhC 病例呈不一致阴性且缺乏 IISNP。作为对照，IISNP 为 30/33 的病例提供了信息。 NIPT MPS 适用于胎儿血型基因分型，并且在一次测试中涵盖多个血型和对照目标。注意到 Rh 系统的谨慎性，这有可能为同种免疫女性提供个性化服务。

更新日期：2023-11-20

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南