title: Validation of copy number variation sequencing for detecting chromosome imbalances in human preimplantation embryos.
abstract: Chromosome aneuploidies commonly arise in embryos produced by assisted reproductive technologies and represent a major cause of implantation failure and miscarriage. Currently, preimplantation genetic diagnosis (PGD) is performed by array-based methods to identify euploid embryos for transfer to the patient. We speculated that a combination of next-generation sequencing technologies and sophisticated bioinformatics would deliver a more comprehensive and accurate methodology to improve the overall efficacy of embryo testing. To meet this challenge, we developed a high-resolution copy number variation (CNV) sequencing pipeline suitable for single-cell analysis. In validation studies, we showed that CNV-Seq was highly sensitive and specific for detection of euploidy, aneuploidy, and segmental imbalances in 24 whole genome amplification samples from PGD embryos that were originally diagnosed by gold standard array comparative genomic hybridization. In addition, CNV-Seq was capable of detecting, mapping, and accurately quantifying terminal chromosome imbalances down to 1 Mb in size originating from abnormal segregation of translocation chromosomes. These validation studies indicate that CNV-Seq displays the hallmarks of an accurate and reliable embryo test with the potential to further improve the overall efficacy of PGD.
authors: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.
authors: Li
authors: L
authors: Wang
authors: Berry Genomics, C., Limited, Beijing, China david.cram@berrygenomics.com.
authors: David S
authors: DS
authors: Cram
authors: State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Jiandong
authors: J
authors: Shen
authors: IVF Center, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors: Xiaohong
authors: X
authors: Wang
authors: Berry Genomics, C., Limited, Beijing, China.
authors: Jianguang
authors: J
authors: Zhang
authors: Berry Genomics, C., Limited, Beijing, China.
authors: Zhuo
authors: Z
authors: Song
authors: Berry Genomics, C., Limited, Beijing, China.
authors: Genming
authors: G
authors: Xu
authors: IVF Center, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors: Na
authors: N
authors: Li
authors: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.
authors: Junmei
authors: J
authors: Fan
authors: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors: Shufang
authors: S
authors: Wang
authors: IVF Center, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors: Yaning
authors: Y
authors: Luo
authors: IVF Center, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors: Jun
authors: J
authors: Wang
authors: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors: Li
authors: L
authors: Yu
authors: State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China jyliu_nj@126.com.
authors: Jiayin
authors: J
authors: Liu
authors: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China yqyaolab@gmail.com.
authors: Yuanqing
authors: Y
authors: Yao
mesh_terms: D000782:Aneuploidy; D001755:Blastocyst; D005307:Fertilization in Vitro; D006801:Humans; D016133:Polymerase Chain Reaction; D019836:Preimplantation Diagnosis / Q000379:methods; D015203:Reproducibility of Results
keywords: array CGH; blastomere biopsy; copy number variation sequencing; embryos; preimplanation genetic diagnosis