2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Analysis of challenging products of conception cases with optical genome mapping: a preliminary study

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This study focuses on the analysis of challenging cases involving products of conception (POC) using optical genome mapping (OGM). The standard genetic testing methods for POC, such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), have limitations and may require multiple tests to reach a genetic diagnosis. Additionally, POC samples are difficult to culture and may have maternal cell contamination (MCC), which makes it challenging to analyze them with standard methods. <br /><br />The researchers used OGM to analyze POC samples that could not be analyzed with standard methods due to high MCC. OGM involves isolating high molecular weight DNA from POC tissue and the mother's peripheral blood cells. The DNA is labeled and loaded onto a Saphyr chip, where it is linearized and imaged at a single molecule resolution. The images are converted to molecular barcodes and mapped to a reference genome for variant calling.<br /><br />OGM was found to be highly sensitive in detecting structural variants (SVs) and improved the genetic diagnostic yield in POC cases. The study supports OGM as a first-tier test for analyzing POC samples.<br /><br />In terms of study design, the researchers compared the variants between POC and mother's blood samples and assessed the MCC by documenting the variant allele frequency (VAF) of unique variants in the POC tissue. The unique variants were characterized based on ACMG guidelines. The mother's sample was also assessed for balanced translocations and inversions.<br /><br />The data analysis included 15 POC cases that had high MCC contamination or no growth and could not be analyzed using standard methods. The OGM data was gathered at a coverage of over 330x and assembled using a rare variant pipeline. The study presented some specific cases with genome copy number profiles and MCC estimates.<br /><br />Overall, the study concludes that OGM is a promising technology for analyzing challenging POC cases and has the potential to improve the genetic diagnostic yield in these cases. The researchers propose a workflow that includes OGM as a first-tier test for POC sample analysis.

Asset Subtitle

Presenting Author - Nikhil S. Sahajpal, PhD; Co-Author - Ashis K. Mondal, PhD; Co-Author - Harmanpreet Singh, PhD; Co-Author - Timothy Fee, PhD; Co-Author - Fatima E. Abidi, PhD, FACMG; Co-Author - Benjamin A. Hilton, PhD; Co-Author - Ravindra Kolhe, MD, PhD.; Co-Author - Barbara R. DuPont, PhD, FACMG;

Meta Tag

Molecular Cytogenetics

Chromosomal Abnormalities

Co-Author Barbara R. DuPont, PhD, FACMG

Co-Author Ravindra Kolhe, MD, PhD.

Co-Author Benjamin A. Hilton, PhD

Co-Author Fatima E. Abidi, PhD, FACMG

Co-Author Timothy Fee, PhD

Co-Author Harmanpreet Singh, PhD

Co-Author Ashis K. Mondal, PhD

Presenting Author Nikhil S. Sahajpal, PhD

Keywords

products of conception

optical genome mapping

genetic testing methods

maternal cell contamination

high molecular weight DNA

structural variants

genetic diagnostic yield

variant allele frequency

ACMG guidelines

data analysis