Expanding the Utility of Exome Sequencing in Preventive and Population Genetics

Carrier screening is a long-standing genetic testing process offered to at-risk couples, with or without a family history, who might have pregnancies affected by an autosomal recessive (AR) or X-linked (XL) disorder. A total of 276 unrelated individuals, initially referred for rare disorder screening by clinicians, were enrolled in this study and tested by Exome sequencing (ES). Expanded carrier screening (ECS) was performed for 176 disorders that met the inclusion criteria of the ACMG and ACOG. Genes with single nucleotide variants (SNVs) identified with a carrier rate > 1% for AR disorders included HBB, CFTR, PMM2, NPHS2, GJB2, ACADM, ALDOB, MEFV, MKS1, NEB, PAH, ATM, CPT2, CYP21A2, AGXT, BBS1, CAPN3, COL4A4, DHCR7, GAA, IVD, LAMA2, SLC22A5, SLC26A4, USH2A. For XL disorders, variants were detected in the RS1 gene. ECS offers a wealth of information about SNVs related to AR and XL disorders in specified populations. The information obtained from ECS provides multiple advantages: (a) it identifies the most prominent risks in health care in a given population and contributes to the prevention of genetic disorders, (b) it enriches available databases with pathogenic or likely pathogenic SNVs, and (c) it records novel targets for molecular clinical genetic testing.