Optical genome mapping for detection of chromosomal aberrations in prenatal diagnosis

Abstract

Introduction: Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool for detecting a broad range of chromosomal aberrations in a single assay, but relevant clinical feasibility studies of optical genome mapping in prenatal diagnosis are limited. Material and methods: We retrospectively performed optical genome mapping analysis of amniotic fluid samples from 34 fetuses with various clinical indications and chromosomal aberrations detected through standard-of-care technologies, including karyotyping, fluorescence in situ hybridization, and/or chromosomal microarray analysis. Results: In total, we analyzed 46 chromosomal aberrations from 34 amniotic fluid samples, including 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, and 1 region of homozygosity. Overall, 45 chromosomal aberrations could be confirmed by our customized analysis strategy. Optical genome mapping reached 97.8% concordant clinical diagnosis with standard-of-care methods for all chromosomal aberrations in a blinded fashion. Compared with the widely used chromosomal microarray analysis, optical genome mapping additionally determined the relative orientation and position of repetitive segments for seven cases with duplications or triplications. The additional information provided by optical genome mapping will be conducive to characterizing complex chromosomal rearrangements and allowing us to propose mechanisms to explain rearrangements and predict the genetic recurrence risk.Conclusions: Our study highlights that optical genome mapping can provide comprehensive and accurate information on chromosomal aberrations in a single test,

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

“…OGM is an emerging and promising cytogenomic technology that has the potential to detect major classes of SVs [3]. Combining microfluidics, automated image analysis and high-resolution microscopy, OGM allows us to detect insertions and deletions above 500 bp in length and other SVs above 30 kbp in length [4]. There are two distinct algorithms.…”

Optical Genome Mapping for Cryptic Chromosomal Rearrangements Identification in Clinical Practice

“…3,4 A growing number of studies have recently demonstrated the efficiency and superiority of OGM in various clinical settings, including both prenatal and postnatal congenital conditions, as well as various hematological and other malignancies. [5][6][7] Here, we explore the value of OGM in identifying cryptic BCRs using a case series from our clinical practice. This study was approved by the ethics committee of the Nanjing Drum Tower Hospital affiliated with Nanjing University Medical School (no.…”

“…Optical genome mapping (OGM), an emerging technology from Bionano Genomics, has a high resolution for detecting nearly all types of genomic SVs and has been recognized as a revolution in next-generation cytogenomic analysis 3,4 . A growing number of studies have recently demonstrated the efficiency and superiority of OGM in various clinical settings, including both prenatal and postnatal congenital conditions, as well as various hematological and other malignancies 5–7 . Here, we explore the value of OGM in identifying cryptic BCRs using a case series from our clinical practice.…”

Application of Optical Genome Mapping to the Genetic Diagnosis of Facioscapulohumeral Muscular Dystrophy 1

“…A genome map is constructed based on the labeling pattern of each strand, and pattern differences detected by comparison with reference data can reveal SVs and large-scale tandem repeat arrays. Studies have applied OGM to diagnose hematologic malignancies [ 3 - 6 ], solid tumors [ 7 , 8 ], and constitutional genetic disorders [ 9 - 12 ].…”