Development of a Novel Next-Generation Sequencing Assay for Carrier Screening in Old Order Amish and Mennonite Populations of Pennsylvania

Publication date: Available online 25 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Erin L. Crowgey, Michael C. Washburn, E. Anders Kolb, Erik G. PuffenbergerGenetically isolated populations such as the Old Order Amish and Old Order Mennonite communities have an increased incidence of specific autosomal recessive disorders due to the founder effect. In these populations, robust expanded carrier screening and diagnostic testing have the potential to reduce overall medical costs and improve patient outcomes. A novel next-generation sequencing assay was developed using anchored multiplex PCR technology (ArcherDX) for 162 different genetic syndromes caused by 202 pathogenic variants consisting of 150 single nucleotide changes, 43 small insertion/deletions, and nine large deletions (>20 nucleotides). In order to assess the accuracy of the screening panel results, 48 samples were selected based on prior whole exome sequencing results. An additional 15 samples were chosen specifically to validate SMN1 and SMN2 copy number analyses. Collectively, the screening panel detected 273 pathogenic single nucleotide or small insertion/deletion variants, 35 copy number variations (CNVs), and one chromosomal abnormality (Klinefelter syndrome). Concordance with prior whole exome sequencing was 100%. By utilizing a novel next-generation sequencing workflow, a successful targeted gene variant panel was developed for the Old Order Amish and Old Order Mennonite populations of Lanc...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research