Deleye Lieselot, Dheedene Annelies, De Coninck Dieter, Sante Tom, Christodoulou Christodoulos, Heindryckx Björn, Van den Abbeel Etienne, De Sutter Petra, Deforce Dieter, Menten Björn, Van Nieuwerburgh Filip
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
Center for Medical Genetics, Ghent University, Ghent, Belgium.
Fertil Steril. 2015 Nov;104(5):1276-85.e1. doi: 10.1016/j.fertnstert.2015.07.1144. Epub 2015 Aug 14.
To add evidence that massive parallel sequencing (MPS) is a valuable substitute for array comparative genomic hybridization (arrayCGH) with a resolution that is more appropriate for preimplantation genetic diagnosis (PGD) in translocation carriers.
Study of diagnostic accuracy.
University hospital.
PATIENT(S): Fifteen patients with a balanced structural rearrangement were included in the study: eight reciprocal translocations, four Robertsonian translocations, two inversions, and one insertional translocation.
INTERVENTION(S): Trophectoderm biopsy was performed on 47 blastocysts.
MAIN OUTCOME MEASURE(S): In the current study, shallow whole genome MPS on a NextSeq500 (Illumina) and Ion Proton (Life Technologies) instrument was performed in parallel on 47 whole genome amplified trophectoderm samples. Data analyses were performed using the QDNAseq algorithm implemented in Vivar.
RESULT(S): In total, 5 normal and 42 abnormal embryos were analyzed. All aberrations previously detected with arrayCGH could be readily detected in the MPS data using both technologies and were correctly identified. The smallest detected abnormality was a ∼ 4.5 Mb deletion/duplication.
CONCLUSION(S): This study demonstrates that shallow whole genome sequencing can be applied efficiently for the detection of numerical and structural chromosomal aberrations in embryos, equaling or even exceeding the resolution of the routinely used microarrays.
补充证据表明大规模平行测序（MPS）是阵列比较基因组杂交（arrayCGH）的一种有价值的替代方法，其分辨率更适合用于易位携带者的植入前基因诊断（PGD）。
诊断准确性研究。
大学医院。
15例有平衡结构重排的患者纳入研究：8例相互易位、4例罗伯逊易位、2例倒位和1例插入易位。
对47个囊胚进行滋养外胚层活检。
在本研究中，在NextSeq500（Illumina）和Ion Proton（Life Technologies）仪器上对47个全基因组扩增的滋养外胚层样本同时进行浅层全基因组MPS。使用Vivar中实现的QDNAseq算法进行数据分析。
共分析了5个正常胚胎和42个异常胚胎。先前用arrayCGH检测到的所有畸变在MPS数据中使用两种技术都能很容易地检测到，并被正确识别。检测到的最小异常是一个约4.5 Mb的缺失/重复。
本研究表明，浅层全基因组测序可有效应用于检测胚胎中的染色体数目和结构畸变，其分辨率等同于甚至超过常规使用的微阵列。
