Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations
Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations
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基于低覆盖率下一代测序的结构重排植入前基因检测可准确区分易位患者的正常胚胎和携带胚胎
DOI：
10.1016/j.rbmo.2022.05.012
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发表时间：
2022-09-01
影响因子：
4
通讯作者：
Yan, Zhiqiang
中科院分区：
文献类型：
--
作者：
Zhai, Fan;Wang, Yun;Yan, Zhiqiang
研究问题：基于低覆盖率下一代测序（NGS）的植入前结构重排基因检测（PGT-SR）能否准确区分相互易位（RecT）和罗伯逊易位（RobT）的正常胚胎和携带者胚胎？设计：共有109对夫妇与RecT或RobT被纳入本研究。记录年龄、不良生育史（BOH）、外周血染色体核型和IVF周期信息，包括卵丘-卵母细胞复合体数、中期II期卵母细胞数、双原核卵母细胞数和囊胚数。0.1在PGT-SR循环中进行胚胎的X全基因组测序（WGS），随后是拷贝数变异（鉴定不平衡/平衡），以及亲本和胚胎的2X WGS，随后是单倍型分析（区分正常和携带者）。移植未易位的胚胎并评估临床结局。结果：在本研究的所有夫妇中，67例患者接受了RectT，42例患者接受了RobT。对103个平衡胚胎进行不平衡和平衡检测后，进一步进行正常和携带者鉴别，鉴定出53个正常胚胎。最终移植正常胚胎32枚，继续妊娠率为46.88%（15/32）。所有正在进行的妊娠进行羊膜穿刺术，羊膜穿刺术核型分析结果显示与PGT-SR diagnosis.Conclusions 100%一致性：我们的低覆盖率基于NGS的PGT-SR方法可以准确地区分正常和平衡胚胎的携带者状态。该方法具有成本效益，具有广泛的临床适用性。
Research question: Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next -generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)?Design: A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus-oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 x whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 x WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. Results: Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis.Conclusions: Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability.