Unlocking the mysteries of the genome is our life’s work. Since the launch of our first clinical genomic test for identifying the genetic cause of rare diseases, we’ve sought ways to leverage our technology and expertise to support clinicians and the patients and families they serve.  

As genomic technologies improve, we gain new tools that enable us to understand the genome in new ways, helping us continue to improve the science of understanding rare disease. Through our Patient for Life program, we continue to provide clinical reporting of findings as we make new discoveries about the relationship between a patient’s genes and their disease.

Ambry Genetics was selected by the GREGoR Consortium (Genomics Research to Elucidate the Genetics of Rare diseases) to support the Pediatric Mendelian Genomics Research Center (MGRC) program. In collaboration with PacBio, we will leverage new, long-read sequencing technology to support the discovery of additional disease-causing genetic conditions, helping us identify and classify variants as we seek to identify a genetic diagnosis for rare disease patients for whom short-read sequencing-based tests have not yielded a result. 

Advancing Genomic Science: Why Sequencing Technology Matters 

Next-generation sequencing technologies have powered Ambry Genetics’ sequencing-based clinical tests since the introduction of these technologies in the late 2000s. These sequencing instruments sequence short fragments of DNA (called short-reads) and then reassemble these using advanced bioinformatics tools. 

Assembling a genome or an exome (the region of the genome that codes for proteins) from these 150 base pair fragments of DNA is like solving a puzzle. Current bioinformatics technologies tend to be able to solve puzzles where the genetic change of interest is a single point mutation, a gene, or sometimes multiple copies of a fragment of DNA but are not as well-suited to solve puzzles where the genetic change involves the structure of the genome itself. 

Our knowledge of genomics to date has largely been built based on information understood from genomes sequenced via short-read sequencing technologies, but we believe there’s more to our collective genomics story than can be understood with short-read sequencing technology alone.

Enter long-read sequencing. Long-read sequencing technology looks at stretches of DNA thousands of base pairs long. By studying the genome in its native form via long-read sequencing, we can more easily identify structural genes present in the DNA such as stretches of DNA that are inverted, rearranged, or located in the wrong place. We can also leverage capabilities of PacBio’s long-read sequencing technology to study the role of epigenomics on disease manifestation.

We believe that the scientific community has underestimated the importance of these types of structural variations and epigenomic changes to rare disease, simply because we haven’t previously had the tools to properly identify and classify them. By participating in research consortia like GREGoR, we will not only help identify genetic causes of disease for specific individuals, but we will also support the scientific community by identifying and cataloging what we learn about the structure and function of genes within the genome. 

What is the GREGoR Consortium? How Will We Collaborate?

The GREGoR Consortium is a National Institutes of Health-funded collaborative effort which aims to identify the underlying genetic cause of rare disease in samples from individuals for whom prior genomic analysis did not yield answers. As one of the largest and most ambitious projects of its kind, the consortium is focusing on developing new insights into rare disease etiology. 

For our part, Ambry Genetics will sequence and analyze data from up to 7,000 human whole genomes over the next three years. We will be working with leading researchers all working together to not only identify the underlying causes of rare diseases, but also to build the community’s knowledge of what whole-genome sequence data generated from long-read sequencing looks like, which is critical to our ability to understand disease-causing genes. 

In addition to clinical reporting of results we obtain, data from this research will be combined with research from other GREGoR sites and shared with the scientific community though the National Human Genome Research Institute’s Analysis Visualization and Informatics Lab-space (AnVIL) platform.

To learn more about the GREGoR Consortium, visit https://gregorconsortium.org/about/gregor-centers.