2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-An Amplification-based, Nanopore Carrier Screening Panel Resolves Clinically-Relevant Variants in CFTR, SMN1/2, HBA1/2, HBB, and FMR1 in a Unified Workflow

An Amplification-based, Nanopore Carrier Screening Panel Resolves Clinically-Relevant Variants in CFTR, SMN1/2, HBA1/2, HBB, and FMR1 in a Unified Workflow

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Pdf Summary

This document summarizes the results of a study on an amplification-based, nanopore carrier screening panel that can detect clinically relevant variants in several genes associated with genetic disorders such as Cystic Fibrosis, Spinal Muscular Atrophy, Hemoglobinopathies, and Fragile X Syndrome. The study aimed to determine if this panel could detect multiple types of variants across these genes in a single workflow. The assay utilized PCR enrichment, copy number variation analysis, and machine learning models to identify SNVs, INDELs, Exon del/dups, SVs, CNVs, and STRs specific to each disease.<br /><br />The study involved testing 168 cell line samples and 249 whole blood samples across seven genes to identify potential carriers of genetic disorders. The results showed that the PCR/nanopore assay accurately identified challenging variants across the tested genes. The assay demonstrated high accuracy in identifying SNVs and INDELs in SMN1, CFTR, HBA1, HBA2, and HBB, as well as SMN1 and SMN2 copy numbers. It also accurately identified FMR1 repeat categories and AGG interruptions, and HBA1/2 SVs.<br /><br />The assay was able to combine at least 96 barcodes in a single run using three PCR enrichment reactions and a unified data processing pipeline. This streamlined workflow could greatly reduce carrier screening complexity and turnaround times when combined with similar assays.<br /><br />The study also demonstrated the assay's performance across different types of samples, including cell line and whole blood samples. The PCR/nanopore assay showed high categorical agreement with orthogonal genotyping methods for various genes, including FMR1, CFTR, SMN1, HBA1/2, and HBB.<br /><br />In summary, the PCR/nanopore carrier screening panel proved to be an effective and efficient method for detecting genetic variants associated with common inherited disorders. It has the potential to simplify carrier screening and improve turnaround times when used in conjunction with other similar assays.

Asset Subtitle

Presenting Author - Bradley Hall, PhD; Co-Author - Bryan Killinger, PhD; Co-Author - Christopher J. Fraher, BS; Co-Author - Bradley Martin, BS, MS, PhD; Co-Author - Monica P. Roberts, MS; Co-Author - Jonathan Turner, MS; Co-Author - Pranesh Rao, MS; Co-Author - Ryan Routsong, MS; Co-Author - Gary J. Latham, PhD;

Meta Tag

Bioinformatics

Genetic Diversity

Genetic Testing

Genomic Methodologies

Polymorphism

Prenatal Diagnosis

Sequencing

Variant Detection

Co-Author Bryan Killinger, PhD

Co-Author Christopher J. Fraher, BS

Co-Author Bradley Martin, BS, MS, PhD

Co-Author Monica P. Roberts, MS

Co-Author Jonathan Turner, MS

Co-Author Pranesh Rao, MS

Co-Author Ryan Routsong, MS

Co-Author Gary J. Latham, PhD

Presenting Author Bradley Hall, PhD

Keywords

amplification-based

nanopore carrier screening panel

genetic disorders

PCR enrichment

copy number variation analysis

SNVs

INDELs

cell line samples

whole blood samples

inherited disorders