Making Whole Genome Sequencing the Universal Genetic Test - with David Ledbetter, Pediatric Rare Disease Institute, FSU

Today we sit down with renowned geneticist David Ledbetter, whose pioneering work helped uncover the chromosomal basis of Prader-Willi, Angelman, and Miller-Dieker syndromes. He served as Chief Scientific Officer at Geisinger, where he led the MyCode Community Health Initiative—one of the largest population genomic screening programs in the world. Now, he's bringing his decades of experience to bear on a bold new initiative: the Institute for Pediatric Rare Diseases at Florida State University.

Funded through Florida’s landmark Sunshine Act, the new institute is part of a broader vision to create a statewide pediatric genetics network and pilot universal newborn whole genome screening. Ledbetter walks us through how this model could reshape not only early diagnosis but the entire standard of care for children with rare genetic conditions.

* 0:00 From 5 to 50% rare disease diagnosis

* 4:00 The MyCode story at Geisinger

* 7:00 Leading the new pediatric rare disease institute at FSA

* 11:20 Moving closer to universal newborn screening

* 20:20 More information is better

* 34:00 WGS as universal platform

Ledbetter is bullish on whole genome sequencing (WGS) as the foundation for future genetic testing:

“Whole genome sequencing is becoming the universal platform for genetic testing. That greatly simplifies testing—physicians no longer need to know dozens of platforms. They just need to provide good clinical info, and we’ll handle the rest.”

He also makes the ethical case for early diagnosis as a matter of patient rights:

“If you really have a genetic technology that can identify every rare genetic disease individual at birth, that child has the right to be found.”

From the cost and logistics of trio testing to the promise of AI in variant interpretation, this conversation offers a powerful glimpse into where rare disease diagnosis is headed—and why Florida may be leading the way.

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