Carrier Screening Assay Developed for Genetically Isolated Populations

A new low-cost genetic test that accurately identified more than 200 known disease-causing gene variations in two high-risk populations, the Old Order Amish and Old Order Mennonites of Lancaster County, Pennsylvania, has been developed by researchers at Nemours Children's Health System. Details were published earlier this week in the Journal of Molecular Diagnostics

"These are genetically isolated communities with a higher incidence of certain disorders," said Erin Crowgey, Ph.D., lead author of the study and associate director for bioinformatics at Nemours. "Robust, expanded screening and diagnostic testing in these populations for people who may carry these gene variants could potentially improve patient outcomes and reduce medical costs, through a single low-cost procedure."

The research team developed a next-generation sequencing test capable of identifying 202 known gene variants, or alleles, associated with 162 conditions found in these Amish and Mennonite communities, also known as Plain communities, to identify carriers of these variants in a simple blood test. To do so, the Clinic for Special Children (CSC), a medical home for uninsured Plain community children with genetic disorders, selected 63 patients to participate by providing blood samples for the DNA analysis.

A targeted gene panel using a custom configuration of the ArcherDX Anchored Multiplexed PCR technology was created. In total, 309 different gene variants were detected. To assess the test's accuracy, they used an alternate method to validate all genetic variants. For instance, they compared 48 samples with prior whole exome sequencing results, and found 100% agreement between the two methods.

"Due to their small number of community founders, the Plain populations over time have come to exhibit relatively high carrier rates for a small set of genetic diseases," said Erik Puffenberger, Ph.D., a study author and laboratory director at CSC. "We needed a methodology for a single procedure to test individuals for all known genetic variations related to those conditions."