PMID- 37732322 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230922 IS - 1664-8021 (Print) IS - 1664-8021 (Electronic) IS - 1664-8021 (Linking) VI - 14 DP - 2023 TI - Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping. PG - 1248755 LID - 10.3389/fgene.2023.1248755 [doi] LID - 1248755 AB - Background and aims: Certain chromosomal structural variations (SVs) in biological parents can lead to recurrent spontaneous abortions (RSAs). Unequal crossing over during meiosis can result in the unbalanced rearrangement of gamete chromosomes such as duplication or deletion. Unfortunately, routine techniques such as karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) cannot detect all types of SVs. In this study, we show that optical genome mapping (OGM) quickly and accurately detects SVs for RSA patients with a high resolution and provides more information about the breakpoint regions at gene level. Methods: Seven couples who had suffered RSA with unbalanced chromosomal rearrangements of aborted embryos were recruited, and ultra-high molecular weight (UHMW) DNA was isolated from their peripheral blood. The consensus genome map was created by de novo assembly on the Bionano Solve data analysis software. SVs and breakpoints were identified via alignments of the reference genome GRCh38/hg38. The exact breakpoint sequences were verified using either Oxford Nanopore sequencing or Sanger sequencing. Results: Various SVs in the recruited couples were successfully detected by OGM. Also, additional complex chromosomal rearrangement (CCRs) and four cryptic balanced reciprocal translocations (BRTs) were revealed, further refining the underlying genetic causes of RSA. Two of the disrupted genes identified in this study, FOXK2 [46,XY,t(7; 17)(q31.3; q25)] and PLXDC2 [46,XX,t(10; 16)(p12.31; q23.1)], had been previously shown to be associated with male fertility and embryo transit. Conclusion: OGM accurately detects chromosomal SVs, especially cryptic BRTs and CCRs. It is a useful complement to routine human genetic diagnostics, such as karyotyping, and detects cryptic BRTs and CCRs more accurately than routine genetic diagnostics. CI - Copyright (c) 2023 Rao, Zhang, Zou, Ma, Huang, Yuan, Zhou, Lu, Li, Huang, Liu and Yang. FAU - Rao, Huihua AU - Rao H AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Zhang, Haoyi AU - Zhang H AD - School of Public Health, Nanchang University, Nanchang, Jiangxi, China. FAU - Zou, Yongyi AU - Zou Y AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Ma, Pengpeng AU - Ma P AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Huang, Tingting AU - Huang T AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Yuan, Huizhen AU - Yuan H AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Zhou, Jihui AU - Zhou J AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Lu, Wan AU - Lu W AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Li, Qiao AU - Li Q AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Huang, Shuhui AU - Huang S AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Liu, Yanqiu AU - Liu Y AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. FAU - Yang, Bicheng AU - Yang B AD - Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. AD - Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. LA - eng SI - figshare/10.6084/m9.figshare.24046965 PT - Journal Article DEP - 20230904 PL - Switzerland TA - Front Genet JT - Frontiers in genetics JID - 101560621 PMC - PMC10507169 OTO - NOTNLM OT - Oxford Nanopore technology (ONT) OT - balanced reciprocal translocation (BRT) OT - complex chromosomal rearrangement (CCR) OT - optical genome mapping (OGM) OT - recurrent spontaneous abortion (RSA) OT - structural variations (SVs) COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/09/21 06:42 MHDA- 2023/09/21 06:43 PMCR- 2023/09/04 CRDT- 2023/09/21 04:16 PHST- 2023/06/27 00:00 [received] PHST- 2023/08/21 00:00 [accepted] PHST- 2023/09/21 06:43 [medline] PHST- 2023/09/21 06:42 [pubmed] PHST- 2023/09/21 04:16 [entrez] PHST- 2023/09/04 00:00 [pmc-release] AID - 1248755 [pii] AID - 10.3389/fgene.2023.1248755 [doi] PST - epublish SO - Front Genet. 2023 Sep 4;14:1248755. doi: 10.3389/fgene.2023.1248755. eCollection 2023.