Optical Genome Mapping for Chromosomal Aberrations Detection—False-Negative Results and Contributing Factors

Yiyun Xu; Qinxin Zhang; Yan Wang; Ran Zhou; Xiuqing Ji; Lulu Meng; Chunyu Luo; An Liu; Jiao Jiao; Hao Chen; Huasha Zeng; Ping Hu; Zhengfeng Xu

doi:10.3390/diagnostics14020165

Diagnostics (Jan 2024)

Optical Genome Mapping for Chromosomal Aberrations Detection—False-Negative Results and Contributing Factors

Yiyun Xu,
Qinxin Zhang,
Yan Wang,
Ran Zhou,
Xiuqing Ji,
Lulu Meng,
Chunyu Luo,
An Liu,
Jiao Jiao,
Hao Chen,
Huasha Zeng,
Ping Hu,
Zhengfeng Xu

Affiliations

Yiyun Xu: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Qinxin Zhang: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Yan Wang: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Ran Zhou: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Xiuqing Ji: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Lulu Meng: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Chunyu Luo: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
An Liu: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Jiao Jiao: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Hao Chen: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Huasha Zeng: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Ping Hu: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China
Zhengfeng Xu: Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Health Care Hospital, Nanjing 210004, China

DOI: https://doi.org/10.3390/diagnostics14020165
Journal volume & issue: Vol. 14, no. 2
p. 165

Abstract

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Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice.

Published in Diagnostics

ISSN: 2075-4418 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Medicine (General)
Website: http://www.mdpi.com/journal/diagnostics

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