Archer at the 2017 ACMG Annual Clinical Genetics Meeting
R. Kulesus | 17 Jan, 2017
American College of Medical Genetics and Genomics
2017 ACMG Annual Clinical Genetics Meeting
March 22 - 25 | Booth 1012
American College of Medical Genetics and Genomics (ACMG) annual meeting provides genetics professionals with the opportunity to learn how genetics and genomics are being integrated into medical or clinical practice.
The latest developments and research in clinical genetics and genomics will be presented.
Rapid and Comprehensive CFTR Variant Profiling Across Ethnic Groups using Anchored Multiplex PCR and Next-Generation Sequencing
Read the abstract
Matthew T. Hardison, PhD, FACMG, Laura M. Griffin, PhD, Brady P. Culver, PhD
Introduction: Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by the build-up of thick mucus resulting in chronic lung infections and airway inflammation. Carrier identification and newborn screening have significant implications in the overall prognosis of CF patients. Underlying CFTR mutations were recently shown to vary significantly across ethnic groups. However, current CFTR genotyping assays detect mutations highly prevalent in white individuals, yet fail to detect mutations that are more prevalent in nonwhite individuals. We present a rapid, cost-effective assay for comprehensive detection of CFTR mutations for pan-ethnic carrier identification and newborn screening.
Methods: BabyGenes, Inc, in partnership with ArcherDX, Inc., has developed a targeted next-generation sequencing (NGS) assay based on Anchored Multiplex PCR (AMP™) to detect mutations in 105 genes clinically linked to inborn errors in metabolism, including CFTR. AMP is a library preparation method for NGS that uses unidirectional gene-specific primers (GSPs) and molecular barcoded adaptors ligated to random start sites to enrich for both known and unknown mutations across a panel of target regions. Following analytical and clinical validation of the panel, a total of 1,585 clinical samples representing a diverse ethnic set were analyzed for clinically significant CFTR variants.
Results: Clinical validation with 150 blinded specimens from the Coriell Institute for Medical Research resulted in 100% accuracy of variant detection within the CFTR gene. Pan-ethnic screening of 1,585 clinical samples identified 34 unique mutations, several of which were identified in multiple individuals. 73% (25/34) of these unique mutations and 60% (74/123) of total mutations detected are not currently included in the ACMG-recommended 23-mutation panel for CF carrier screening. Furthermore, this screening revealed ethnic differences in clinically significant CFTRvariants and a pan-ethnic carrier rate of approximately 7%.
Conclusions: We demonstrate that the BabyGenes, Inc. AMP-based targeted NGS assay enables rapid, highly sensitive, and comprehensive detection of both known and novel mutations in the CFTR gene. This is critical for global carrier and newborn screening, as CF driver mutations have not been fully characterized across all ethnicities. Findings suggest that the pan-ethnic carrier rate of CF may be higher than originally predicted. As this entire assay can be performed in under 96 hours and the reagents do not require refrigeration, AMP is a practical and economical method for global communities.
Archer's newest assays
Reveal ctDNA Kit
Mutation profiling from circulating tumor DNA in liquid biopsies
The Archer® Reveal ctDNA™ 28 Kit for Illumina® is an advanced and user-friendly solution for targeted NGS of circulating cell-free tumor DNA e.g., ctDNA, ccfDNA, cfDNA from 28 genes commonly found mutated in solid tumor type cancers.
Immune repertoire sequencing assays
Archer® Immunoverse™ kits are targeted NGS assays to characterize the human immune repertoire from RNA input. Powered by AMP, the lyophilized kits uniquely tag and amplify V(D)J rearrangements for sequencing on Illumina® platforms.
Comprehensive mutation profiling for cystic fibrosis
The Archer® VariantPlex® CFTR kit is a targeted NGS assay for comprehensive detection of known and unknown variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
ArcherDX addresses the bottlenecks associated with using NGS by offering a robust platform for targeted sequencing applications.Archer target enrichment assays utilize AMP chemistry to generate highly enriched sequencing libraries for comprehensive profiling of fusions, CNVs, SNVs and indels. Amplification from independent, unidirectional primers and universal molecular barcoded adapters permit identification of novel gene fusions and mutations with nucleotide-level resolution. Requiring only one intact primer-binding site, AMP chemistry is uniquely suited to amplify small, degraded fragments, enabling solid tumor mutation profiling from FFPE samples and liquid biopsies. Archer’s easy-to-use, lyophilized kits generate sequencing-ready libraries from RNA, DNA, and liquid biopsy-derived ctDNA. Complemented by the Archer suite of assay design and bioinformatics analysis, Archer’s FusionPlex, VariantPlex and Reveal ctDNA assays facilitate complex mutation identification and discovery, while Immunoverse assays enable quantitative profiling of the expressed immune repertoire.