A Novel Bioinformatic Approach for Large Deletion Detection in Multiplex Pcr-Based Ngs Assays

Fatemeh Abbaszadeh^*, Shaza Abu Sirriya, Bincy Mathew, Ramin Badii, Vasiliki Chini, Zafar Nawaz & Susanna Akiki

Diagnostic Genomic Division, Department of Laboratory Medicine & Pathology, Qatar Rehabilitation Institute (QRI), Hamad Medical Corporation (HMC), Hamad Bin Khalifa Medical City, Doha-Qatar

Dr. Fatemeh Abbaszadeh, Diagnostic Genomic Division, Department of Laboratory Medicine & Pathology, Qatar Rehabilitation Institute (QRI), Hamad Medical Corporation (HMC), Hamad Bin Khalifa Medical City, Doha-Qatar.

Keywords: Multiplex PCR; NGS; Long Deletion; BRCA1; OBRA

Abstract

Background
Next-generation sequencing (NGS) has changed genetic diagnostics due to its high throughput, speed, and cost-effectiveness. This paper describes the challenges that were faced in detection of the frameshift variant c.1175_1214del in the BRCA1 gene, undetectable by CNV analysis, using Oncomine BRCA Research Assay (OBRA) and Ion Torrent platform. This paper also describes the bioinformatic strategy implemented to successfully detect and annotate this large deletion. Frameshift variants comprise the highest proportion (>60%) of pathogenic variants identified in BRCA1/2 genes and a false negative BRCA1/2 result leads to the provision of inaccurate genetic counseling and has negative impacts on medical management and risk assessment for BRCA-related cancer patients and their at-risk relatives.

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