Enhanced Structural Variation Detection with Optical Genome Mapping in Constitutional Genetic Disorders.

Identification and detection of structural variations (SVs), copy number variations (CNVs), and tandem repeat expansions/contractions has been the standard of care (SOC) for the detection and diagnosis of constitutional genetic disorders (prenatal and postnatal setting). Current SOC methods have limitations that include low resolution (karyotyping), inability to interrogate the whole genome (FISH), and inability to detect balanced SVs and orientation of duplicated segments of genome (chromosomal microarrays). Other molecular methods utilized for repeat expansion/contraction disorders are time-consuming and laborious (southern blotting) or have a low dynamic range (PCR, NGS). Optical genome mapping (OGM) has emerged as a technology that enables the detection of several classes of SVs, CNVs and repeat array analyses in a single workflow. At Augusta University, we performed a clinical evaluation and validation of OGM for constitutional genetic disorders in 196 samples that included 85 prenatal specimens (cultured amniocytes) and 106 postnatal specimens (peripheral blood/cryopreserved or cultured cell lines). Our results were 100% concordant with SOC and demonstrated a smooth laboratory workflow for different sample types. The inter- and intra-run studies were performed on a subset of samples and the reproducibility data was 100% concordant.