Whole genome sequencing strains, then reshapes rare diagnosis

Whole genome sequencing is gaining ground as the first-line tool for rare disease diagnosis, with professional guidance supporting its use across several clinical indications. Yet coverage gaps and a persistent diagnostic reality—WGS won’t solve every case—are

A rare-disease diagnosis can take five or more years in the United States. For roughly one in 10 Americans living with such conditions, the journey is often a long stretch of appointments, expensive tests, and uncertainty—until a clear answer finally arrives.

That timeline is where the urgency sits for Baylor Genetics’ chairman and CEO, Kengo Takishima. He argues healthcare advances only when scientific breakthroughs move into day-to-day patient care, shortening the wait for answers that families are pursuing with every appointment and test.

The push is for a “genome-first” approach built around whole genome sequencing (WGS) as standard of care. The goal is simple in concept but hard in practice: use WGS early as a first-line tool for all patients. so people get access to comprehensive testing earlier in the diagnostic journey—when it can be most impactful.

WGS is already recommended across multiple professional society guidelines for clinical indications including intellectual disability. developmental delay. congenital anomalies. and unexplained epilepsy. But Takishima says the system is moving faster than the coverage rules. In March 2026, Baylor Genetics’ internal data found that approximately 58% of U.S. commercial payers and 73% of Medicaid programs provide coverage for WGS in outpatient settings.

The mismatch creates a stubborn bottleneck: recognition grows in the medical community. yet broad access still depends on whether insurance will pay. Takishima frames the remaining work as systemic—accelerating access to testing. supporting clinical implementation. increasing insurance coverage. and expanding clinical guidelines.

WGS’s appeal starts with performance. It consistently demonstrates the highest diagnostic yield compared with whole exome sequencing and panel-based genetic testing. with reported diagnostic yields ranging from 27% to 43%. Its strength is breadth, including analysis of up to 98% of the genome. That range can translate into deeper insight into disease mechanisms, informing more accurate diagnoses and supporting clinical care decisions.

Still, WGS is not a universal key. The genome is complex, and Takishima acknowledges that WGS will not diagnose every patient because of inherent biological and technical limitations. That reality leaves a persistent diagnostic gap.

Closing it, he argues, requires a more comprehensive strategy—starting with WGS as a foundation and layering complementary technologies in a selective, targeted way. Difficult-to-map genomic regions and variants with uncertain clinical significance are where additional methods can matter most.

He points to technologies that can expand WGS’s clinical impact. including RNA sequencing. optical genome mapping (OGM). and long-read sequencing (LRS). Used together. the approach is meant to enrich interpretation and uncover deeper genetic insights. offering clearer answers for patients who still need them.

The same logic extends to patients who already received negative or unclear WGS results years ago. Takishima highlights the role of innovation after the test: reanalysis. By reassessing genetic data alongside new phenotypic information. research. insights. and/or analysis tools. reanalysis can reveal developments that were not available at the time of the first test.

That reassessment can include whether a new gene-disease association has been discovered. or whether patients might now be candidates for complementary technologies introduced after the original testing—such as OGM and LRS. For families who remained undiagnosed, this process can reopen the chance of meaningful answers.

Taken together, the message is that rare disease diagnostics can’t be defined by a single test. Progress will depend on how effectively technologies are combined—using WGS as a first-line foundation, adding targeted modalities when the gaps appear, and revisiting data as science evolves.

Takishima says the past decade’s progress has been remarkable, but the work ahead remains urgent. His position is that the system should be designed to turn data into diagnoses—and diagnoses into meaningful care—more consistently than it does today for the millions navigating uncertainty.

rare disease diagnosis whole genome sequencing WGS Baylor Genetics insurance coverage Medicaid commercial payers optical genome mapping long-read sequencing RNA sequencing diagnostic yields reanalysis