PMID- 37543218
OWN - NLM
STAT- MEDLINE
DCOM- 20230913
LR  - 20230913
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 884
DP  - 2023 Oct 30
TI  - Detection of complex chromosome rearrangements using optical genome mapping.
PG  - 147688
LID - S0378-1119(23)00529-2 [pii]
LID - 10.1016/j.gene.2023.147688 [doi]
AB  - Chromosomal structural variations (SVs) are a main cause of human genetic 
      disease. Currently, karyotype, chromosomal microarray analysis (CMA), and 
      fluorescent in situ hybridization (FISH) form the backbone of current routine 
      diagnostics (CRD). These methods have their own limitations. CRD cannot identify 
      cryptic balanced SVs and complex SVs even if these techniques were performed 
      either simultaneously or in a sequential manner. Optical genome mapping (OGM) is 
      a novel technology that can identify several classes of SVs with higher 
      resolution, but studies on the applicability of OGM and its comparison with CRD 
      are inadequate for difficult and complicated chromosomal SVs are lacking. Herein, 
      seven patients with definite complicated SVs involving at least two breakpoints 
      (BPs) were recruited for this study. The results of BPs and SVs from OGM were 
      compared with those from CRD. The results showed that all BPs of five samples and 
      partial BPs of two samples were detected by OGM. The undetected BPs were all 
      close to the repeat-rich gap region. Besides, OGM also detected additional SVs 
      including a cryptic balanced translocation, two additional complex chromosomal 
      rearrangement (CCR). OGM yielded the additional information, such as the 
      orientation of acentric fragments, BP positions, and genes mapped in the BP 
      region for all the cases. The accuracy of additional SVs and BPs detected by OGM 
      was verified by FISH panel and next-generation sequencing and Sanger sequencing. 
      Taken together, OGM exhibit a better performance in detecting chromosomal SVs 
      compared to the CRD. We suggested that OGM method should be utilized in the 
      clinical examination to improve the efficiency and accuracy of genetic disease 
      diagnosis, supplemented by FISH or karyotyping to compensate for the SVs in the 
      repeat-rich gap region if necessary.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Qu, Jiangbo
AU  - Qu J
AD  - Center for Medical Genetics and Prenatal Diagnosis, Key Laboratory of Birth 
      Defect Prevention and Genetic Medicine of Shandong Health Commission, Key 
      Laboratory of Birth Regulation and Control Technology of National Health 
      Commission of China, Shandong Provincial Maternal and Child Health Care Hospital 
      Affiliated to Qingdao University, Jinan 250014, Shandong, China. Electronic 
      address: jbq0315@163.com.
FAU - Li, Shuo
AU  - Li S
AD  - Genetic Testing Center, Qingdao Women and Children's Hospital, Qingdao 266034, 
      Shandong, China. Electronic address: surelee@126.com.
FAU - Yu, Dongyi
AU  - Yu D
AD  - Center for Medical Genetics and Prenatal Diagnosis, Key Laboratory of Birth 
      Defect Prevention and Genetic Medicine of Shandong Health Commission, Key 
      Laboratory of Birth Regulation and Control Technology of National Health 
      Commission of China, Shandong Provincial Maternal and Child Health Care Hospital 
      Affiliated to Qingdao University, Jinan 250014, Shandong, China. Electronic 
      address: dongyi_yu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230803
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
SB  - IM
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Chromosome Aberrations
MH  - *Gene Rearrangement
MH  - Chromosome Mapping/methods
MH  - Chromosomes
OTO - NOTNLM
OT  - Breakpoints
OT  - Chromosomal structure variant
OT  - Complex chromosomal rearrangements
OT  - Optical genome mapping (OGM)
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/08/06 05:42
MHDA- 2023/09/13 06:41
CRDT- 2023/08/05 19:15
PHST- 2023/05/20 00:00 [received]
PHST- 2023/07/15 00:00 [revised]
PHST- 2023/08/02 00:00 [accepted]
PHST- 2023/09/13 06:41 [medline]
PHST- 2023/08/06 05:42 [pubmed]
PHST- 2023/08/05 19:15 [entrez]
AID - S0378-1119(23)00529-2 [pii]
AID - 10.1016/j.gene.2023.147688 [doi]
PST - ppublish
SO  - Gene. 2023 Oct 30;884:147688. doi: 10.1016/j.gene.2023.147688. Epub 2023 Aug 3.