Carrier Screening Assay for Plain Populations

Genetically 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 (AMP™) technology (ArcherDX) for 162 different genetic syndromes caused by 202 pathogenic variants consisting of 150 single nucleotide changes, 43 small insertion/deletions, and 9 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 (WES) 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 WES 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 Lancaster County, Pennsylvania. Population-wide carrier screening may help decrease the morbidity and mortality of these conditions in these high-risk populations.