PMID- 27491356 OWN - NLM STAT- MEDLINE DCOM- 20170630 LR - 20170630 IS - 1399-0004 (Electronic) IS - 0009-9163 (Linking) VI - 91 IP - 4 DP - 2017 Apr TI - Clinical application of whole-genome low-coverage next-generation sequencing to detect and characterize balanced chromosomal translocations. PG - 605-610 LID - 10.1111/cge.12844 [doi] AB - Individuals carrying balanced translocations have a high risk of birth defects, recurrent spontaneous abortions and infertility. Thus, the detection and characterization of balanced translocations is important to reveal the genetic background of the carriers and to provide proper genetic counseling. Next-generation sequencing (NGS), which has great advantages over other methods such as karyotyping and fluorescence in situ hybridization (FISH), has been used to detect disease-associated breakpoints. Herein, to evaluate the application of this technology to detect balanced translocations in the clinic, we performed a parental study for prenatal cases with unbalanced translocations. Eight candidate families with potential balanced translocations were investigated using two strategies in parallel, low-coverage whole-genome sequencing (WGS) followed-up by Sanger sequencing and G-banding karyotype coupled with FISH. G-banding analysis revealed three balanced translocations, and FISH detected two cryptic submicroscopic balanced translocations. Consistently, WGS detected five balanced translocations and mapped all the breakpoints by Sanger sequencing. Analysis of the breakpoints revealed that six genes were disrupted in the four apparently healthy carriers. In summary, our result suggested low-coverage WGS can detect balanced translocations reliably and can map breakpoints precisely compared with conventional procedures. WGS may replace cytogenetic methods in the diagnosis of balanced translocation carriers in the clinic. CI - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Liang, D AU - Liang D AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Wang, Y AU - Wang Y AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Ji, X AU - Ji X AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Hu, H AU - Hu H AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Zhang, J AU - Zhang J AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Meng, L AU - Meng L AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Lin, Y AU - Lin Y AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Ma, D AU - Ma D AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Jiang, T AU - Jiang T AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Jiang, H AU - Jiang H AD - Clinical Laboratory of BGI Health, BGI, Shenzhen, China. FAU - Asan AU - Asan AD - Binhai Genomics Institute, BGI-Tianjin, BGI-shenzhen, Tianjin, China. AD - Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, China. FAU - Song, L AU - Song L AD - Binhai Genomics Institute, BGI-Tianjin, BGI-shenzhen, Tianjin, China. AD - Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, China. FAU - Guo, J AU - Guo J AD - Binhai Genomics Institute, BGI-Tianjin, BGI-shenzhen, Tianjin, China. AD - Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, China. FAU - Hu, P AU - Hu P AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Xu, Z AU - Xu Z AD - State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article DEP - 20160905 PL - Denmark TA - Clin Genet JT - Clinical genetics JID - 0253664 SB - IM MH - Abnormalities, Multiple/diagnosis/*genetics/pathology MH - Adult MH - Chromosome Disorders/diagnosis/*genetics/pathology MH - Cytogenetic Analysis MH - Female MH - Genetic Counseling MH - *High-Throughput Nucleotide Sequencing MH - Humans MH - In Situ Hybridization, Fluorescence MH - Karyotyping MH - Mothers MH - Polymorphism, Single Nucleotide MH - Translocation, Genetic/*genetics OTO - NOTNLM OT - balanced chromosomal translocation OT - chromosomal microarray OT - fluorescence in situ hybridization OT - high-throughput nucleotide sequencing OT - karyotyping OT - prenatal diagnosis EDAT- 2016/08/06 06:00 MHDA- 2017/07/01 06:00 CRDT- 2016/08/06 06:00 PHST- 2016/05/18 00:00 [received] PHST- 2016/07/31 00:00 [revised] PHST- 2016/08/01 00:00 [accepted] PHST- 2016/08/06 06:00 [pubmed] PHST- 2017/07/01 06:00 [medline] PHST- 2016/08/06 06:00 [entrez] AID - 10.1111/cge.12844 [doi] PST - ppublish SO - Clin Genet. 2017 Apr;91(4):605-610. doi: 10.1111/cge.12844. Epub 2016 Sep 5.