Optical genome mapping for prenatal diagnosis: A prospective study

Goumy, Carole; Guy Ouedraogo, Zangbéwendé; Soler, Gwendoline; Eymard-Pierre, Eleonore; Laurichesse, Hélène; Delabaere, Amélie; Gallot, Denis; Bouchet, Pamela; Perthus, Isabelle; Pebrel-Richard, Céline; Gouas, Laetitia; Salaun, Gaëlle; Salse, Jérôme; Véronèse, Lauren; Tchirkov, Andrei

doi:10.1016/j.cca.2023.117594

Cited by 8 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, OGM failed to detect 10 (6.5%, 10/154) chromosomal aberrations taking GRCh37 as the reference genome, including five CNVs, two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). Compared with previous studies, the concordance rate in our study was slightly lower [5,6,19]. The main reason is that previous studies excluded the aberrations with (peri)centromeric breakpoints or VAF < 5%.…”

Section: Discussioncontrasting

confidence: 80%

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

Xu,

Zhang,

Wang

et al. 2024

Diagnostics

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 80%

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

Xu,

Zhang,

Wang

et al. 2024

Diagnostics

View full text Add to dashboard Cite

show abstract

“…The de novo assembly and variant annotation pipeline were executed with Bionano Solve software v.1.7, as previously described [9].…”

Section: De Novo Assembly Structural Variant Calling and Data Analysismentioning

confidence: 99%

Feasibility of Optical Genome Mapping from Placental and Umbilical Cord Sampled after Spontaneous or Therapeutic Pregnancy Termination

Goumy,

Ouedraogo,

Bellemonte

et al. 2023

Diagnostics

Self Cite

View full text Add to dashboard Cite

Optical genome mapping (OGM) is an alternative to classical cytogenetic techniques to improve the detection rate of clinically significant genomic abnormalities. The isolation of high-molecular-weight (HMW) DNA is critical for a successful OGM analysis. HMW DNA quality depends on tissue type, sample size, and storage conditions. We assessed the feasibility of OGM analysis of DNA from nine umbilical cord (UC) and six chorionic villus (CV) samples collected after the spontaneous or therapeutic termination of pregnancy. We analyzed quality control metrics provided by the Saphyr system (Bionano Genomics) and assessed the length of extracted DNA molecules using pulsed-field capillary electrophoresis. OMG data were successfully analyzed for all six CV samples. Five of the UC samples did not meet the Saphyr quality criteria, mainly due to poor DNA quality. In this regard, we found that DNA quality assessment with pulsed-field capillary electrophoresis can predict a successful OGM analysis. OGM data were fully concordant with the results of standard cytogenetic methods. Moreover, OGM detected an average of 14 additional structural variants involving OMIM genes per sample. On the basis of our results, we established the optimal conditions for sample storage and preparation required for a successful OGM analysis. We recommend checking DNA quality before analysis with pulsed-field capillary electrophoresis if the storage conditions were not ideal or if the quality of the sample is poor. OGM can therefore be performed on fetal tissue harvested after the termination of pregnancy, which opens up the perspective for improved diagnostic yield.

show abstract

“…Recently, optical genome mapping (OGM) has emerged as a next‐generation cytogenomic tool for the comprehensive analysis of structural variants (SVs) (Sahajpal et al., n.d.; Goumy et al., 2023; Mantere et al., 2021; Sahajpal et al., 2021). OGM provides a high level of genome coverage, ultra‐high resolution, a low false call rate and ease of analysis (Sahajpal et al., n.d.; Dremsek et al., 2021; Goumy et al., 2023; Mantere et al., 2021; Sahajpal et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling

Bouassida,

Molina‐Gomes,

Koraichi

et al. 2024

Molec Gen & Gen Med

View full text Add to dashboard Cite

BackgroundDespite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy‐number‐variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements.Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations.MethodsHere, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene.ResultsOGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow‐up and familial screening appropriately.ConclusionAlong with an increase in diagnostic rates, OGM can rapidly highlight genotype–phenotype correlations, improve genetic counselling and significantly influence prenatal management.

show abstract

Optical genome mapping for prenatal diagnosis: A prospective study

Cited by 8 publications

References 33 publications

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

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

Feasibility of Optical Genome Mapping from Placental and Umbilical Cord Sampled after Spontaneous or Therapeutic Pregnancy Termination

The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling

Contact Info

Product

Resources

About