Applications of genome sequencing as a single platform for clinical constitutional genetic testing

Abstract

The number of human disease genes has dramatically increased over the past decade, largely fueled by ongoing advances in sequencing technologies. In parallel, the number of available clinical genetic tests has also increased, including the utilization of exome sequencing for undiagnosed diseases. Although most clinical sequencing tests have been centered on enrichment-based multigene panels and exome sequencing, the continued improvements in performance and throughput of genome sequencing suggest that this technology is emerging as a potential platform for routine clinical genetic testing. A notable advantage is a single workflow with the opportunity to reflexively interrogate content as clinically indicated; however, challenges with implementing routine clinical genome sequencing still remain. This review is centered on evaluating the applications of genome sequencing as a single platform for clinical constitutional genetic testing, including its potential utility for diagnostic testing, carrier screening, cytogenomic molecular karyotyping, prenatal testing, mitochondrial genome interrogation, and pharmacogenomic and polygenic risk score testing.