For Rare Disease, What’s Missed by Genome Sequencing Still Matters

For almost two decades, members of the life science community bemoaned something that most outsiders never realized: that the “finished” human genome assembly had never actually been finished. Now, thanks to remarkable efforts from the Telomere-to-Telomere (T2T) consortium, we finally have a complete human reference genome. It includes the 8% of the genome that had been impossible to sequence accurately despite many attempts to do so over the years.

What we have learned from the T2T assembly—and from many efforts in the past 20 years to resolve genomic regions that proved impenetrable to conventional sequencing technologies—is that these missing elements matter. Intractable regions...