Illumina's New Mapped Read Technology Provides Insights into Rare Disease: Stephen Kingsmore, Olivia Kim-McManus and Ali Crawford

“We have been talking now for 15, 20 years about the diagnostic odyssey. That shouldn’t exist anymore. The new odyssey is the therapeutic odyssey.”

That’s Stephen Kingsmore, president and CEO of Rady Children’s Hospital (he just announced his retirement), explaining the impact of a new genome mapping technology from Illumina.

Whole-genome sequencing has transformed diagnosis, but some of the hardest pediatric cases persist because the structure of the genome has remained difficult to resolve. Today on Mendelspod, we cover Illumina’s newly launched proximity mapped reads, showing how long-range genomic context can be captured directly on existing Illumina sequencers and integrated into the lab workflow. The conversation traces how this added structural clarity is already improving diagnostic confidence and, critically, enabling highly precise n-of-1 therapies such as antisense oligonucleotides (ASOs).

Olivia Kim-MacManus, a pediatric neurologist and ASO trial leader, shows how the new diagnostic precision directly feeds therapeutic design.

“All of these genetic therapy approaches hinge on precise diagnostics,” she notes, emphasizing that allele-specific and haplotype-aware targeting is essential for ASOs and other emerging gene-based interventions.

From the product and workflow side, Ali Crawford joins us as Senior Director of Science Research at Illumina, detailing how the technology works without requiring new instruments or complex workflows, eliminating the need for separate library preparation steps.

“You just order the kit and go,” she says, highlighting how preserving spatial information on the flow cell unlocks variant calls and structural insight that were previously inaccessible with their standard short-read sequencing.

When genome structure comes into better focus, treatments are no longer theoretical.

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