Genomic Insights / Rare Disease

Leading Global Efforts to Understand and Diagnose Rare Disease

Article originally published by Hannes Smarason's blog - 27/10/2017
By Hannes Smarason

WuXi NextCODE Genomes for Breakfast panel at ASHG 2017

At the ASHG 2017 "Genomes for Breakfast" breakout sessions, panelists discuss how population genomics and rare disease diagnostics are advancing public health.

November 1, 2017 –

At the ASHG 2017 meeting in Orlando, Florida, WuXi NextCODE hosted “Genomes for Breakfast” breakout sessions. Two of these sessions focused specifically on rare diseases, one from a population perspective and the other from a clinical perspective.

We were honored to host speakers who are all leaders in their fields, from distinguished longstanding and newer partners as well as some of our own WuXi NextCODE colleagues. The Genomes for Breakfast events had near-capacity crowds of some 300 attendees. That setting provided an inspirational showcase of progress in understanding rare disease and also how WuXi NextCODE’s global platform can help accelerate this critical work.

INSIGHTS FROM DECODE’S ICELAND GENOMIC SEQUENCING PROJECT

Kari Stefansson kicked off the population genomics session with a deep dive into what he has gleaned from looking at the unique genetics resources he has amassed at deCODE genetics in Iceland over the past 20 years. These resources are of astonishing scale, including the directly sequenced whole genomes of nearly 50,000 Icelanders and 10,000 others; imputed whole genome from 400,000 Icelanders; and SNP data from nearly a million people around the world.

This year, Kari received the William Allen Award, the ASHG’s highest honor, so the work he and his deCODE colleagues have achieved was featured at several points the conference. Underscoring the reach and global outlook of deCODE’s work, Kari pointed out that deCODE is currently collaborating with over 250 international groups and 25 consortia.

His talk was particularly significant for us, because deCODE is not only the world’s first and largest population genomics effort, it is also the crucible in which our technology was forged and the inspiration for the large-scale genomics efforts that we partner with around the world.

USING POPULATION GENOMICS TO UNDERSTAND COMMON AND RARE DISEASES

Leading off the first breakfast session, entitled “Using Population Genomics to Understand Common and Rare Diseases,” Kari spoke to how deCODE has set out to capture and correlate not just variation in the genome and phenome, but also how genetic diversity itself is actually generated.

He pointed out that you could look at life forms as entities whose function is to protect DNA, rather than the other way around. Understanding how DNA changes through generations is a mission-critical task for applying genomics to human health. Where are the sites of the most recombination? Under what circumstances and where are you most likely to see de novo mutations arise?

REACHING 99% ACCURACY IN SEQUENCING THE HUMAN GENOME

A pivotal 2002 paper from deCODE provided the world with the first high-resolution recombination map of the entire genome. That map was used to complete the assembly of the Human Genome Project (HGP). Before that paper was published, the HGP’s assembly was about 91% accurate. After the data from deCODE were incorporated, the map reached 99% accuracy.

DISCOVERIES IN RARE GENE VARIANTS CAN HAVE BROADER PUBLIC HEALTH IMPACT

One of Kari’s observations was that all physiological function is spread across populations in an essentially normal distribution. Looking at extremes—the rare phenotypes—is important, because they often reflect rare genetic factors that can reveal important information.

By studying rare phenotypes, we can draw conclusions about biochemical pathways relevant not only to those carrying the mutations, but also to the rest of the population that has more common, but less extreme, perturbations in those pathways.

In this sense, rare variant identification is important for public health in two ways: to diagnose and better treat those with rare disorders, and to find drug targets that can benefit all of us. Rare disease, it turns out, is a common challenge that we all need to meet together.