title: The clinical utility of next-generation sequencing for identifying chromosome disease syndromes in human embryos.
abstract: Next-generation sequencing is emerging as a reliable and accurate technology for pre-implantation genetic diagnosis (PGD) of aneuploidies and translocations. The aim of this study was to extend the clinical utility of copy number variation sequencing (CNV-Seq) to the detection of small pathogenic copy number variations (CNVs) associated with chromosome disease syndromes. In preliminary validation studies, CNV-Seq was highly sensitive and specific for detecting small CNV in whole-genome amplification products from three replicates of one and five cell samples, with a resolution in the order of 1-2 Mb. Importantly, the chromosome positions of all CNV were correctly mapped with copy numbers similar to those measured in matching genomic DNA samples. In seven clinical PGD cycles where results were obtained for 34 of 35 blastocysts, CNV-Seq identified 18 blastocysts with aneuploidies, one with an aneuploidy and a 4.98 Mb 5q35.2-qter deletion associated with Sotos syndrome, one with a 6.66 Mb 7p22.1-pter deletion associated with 7p terminal deletion syndrome and 14 with no detectable abnormalities that were suitable for transfer. On the basis of these findings, CNV-Seq displays the hallmarks of a comprehensive PGD technology for detection of aneuploidies and CNVs that are known to affect the development and health of patient's embryos.
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxin Road, Haidian District, Beijing 100853, China.
authors.forename: Junmei
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxin Road, Haidian District, Beijing 100853, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxin Road, Haidian District, Beijing 100853, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxin Road, Haidian District, Beijing 100853, China.
authors.forename: Minyue
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxin Rd, Haidian District, Beijing 100853, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxin Road, Haidian District, Beijing 100853, China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Berry Genomics, C., limited, Building 9, No 6. Jingshun East Street, Chaoyang District, Beijing 100015, China.
authors.forename: Genming
authors.initials: G
authors.lastname: Xu
authors.affiliation: Berry Genomics, C., limited, Building 9, No 6. Jingshun East Street, Chaoyang District, Beijing 100015, China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Berry Genomics, C., limited, Building 9, No 6. Jingshun East Street, Chaoyang District, Beijing 100015, China. Electronic address: david.cram@berrygenomics.com.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxin Road, Haidian District, Beijing 100853, China. Electronic address: yqyao_ghpla@163.com.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000782:Aneuploidy; D025063:Chromosome Disorders / Q000175:diagnosis*; D056915:DNA Copy Number Variations; D004622:Embryo, Mammalian / Q000502:physiology*; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D019836:Preimplantation Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity
keywords: aneuploidy; chromosome disease; copy number variation (CNV); next generation sequencing (NGS); whole genome amplification (WGA)