One Million Genomes Meeting Discusses Progress and Promise of Population-Scale Genomics

 
The PacBio team was honored to attend an excellent Keystone Symposium in Hannover, Germany recently. The event, “One Million Genomes: From Discovery to Health,” offered a rare look at large-scale human genome projects, with many top-notch speakers.
The meeting featured speakers from many national genomics efforts, including China, Estonia, Israel, the UK, and the US.  Each of these individual national efforts is essential to overcome the representation bias seen in human genome databases today. Underrepresented groups are currently less likely to get actionable results from clinical genetic tests, a situation that threatens to confer the benefits of precision medicine disproportionately to people of European ancestry. Many of the new population projects have incorporated SMRT Sequencing, either to produce a reference-grade de novo assembly or to generate structural variation data about participants of diverse ancestry.

A highlight of the meeting for us was the closing talk from Jeong-Sun Seo of Seoul National University Bundang Hospital and Macrogen in South Korea. Professor Seo discussed the GenomeAsia 100K Project and Asian reference genomes.  Seo reported on three de novo, reference-grade Asian genomes – Chinese HX1, Japanese JRGv1, and Korean AK1 – all generated with SMRT Sequencing. These genomes enable more accurate re-sequencing of 4.5 billion Asian people, which Seo explained is useful to detect medically relevant variants in this population. At the time of publication, the AK1 genome was the most contiguous personal human genome ever reported, with a contig N50 over 18 Mb.
Seo also presented initial results from a new project that is using PacBio sequencing to detect structural variants in 300 Mongolian individuals. He observed that more of the structural variants in AK1 were detected with PacBio sequencing of the first 30 Mongolian individuals than had been seen in 2,504 individuals from the 1000 Genomes Project, which relied on short-read sequencing. This likely reflects two factors: Asian-specific variation and the greatly increased sensitivity of PacBio sequencing for structural variants.
Also at the event, PacBio scientist Ralph Vogelsang presented a poster about population-scale discovery of structural variants that showed how SMRT Sequencing is uniquely suited to detecting large and often complex variants, which are known to cause disease but are frequently missed by short-read sequencing approaches. The poster also includes a helpful map of ongoing population-focused genome projects.
Congratulations to all of the scientists around the world contributing to these important efforts. We look forward to seeing the many new discoveries they enable!