FROM THE LABS: How GREGoR Consortium is advancing the diagnostics of rare diseases
Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium in 2021 with the goal of finding molecular diagnoses for individuals with rare diseases who remain undiagnosed after clinical testing – to solve the unsolved. Baylor College of Medicine is one of five clinical sites in the consortium. A new paper published in Nature reviews the major accomplishments of the consortium’s first five years and the frontiers in genomic medicine that researchers will tackle next.
Rare diseases are collectively common and affect approximately 1 in 20 people worldwide.
Advances in genomic sequencing, in particular the widespread use of exome sequencing, and computational analysis have improved rare disease diagnostics. To date, more than 5,000 protein-coding genes have been implicated in disease.
Identifying genes linked to rare diseases
“Identifying the genes underlying rare disease remains the most powerful gateway to the understanding of basic molecular processes in humans,” said Dr. Richard Gibbs, director of the Human Genome Sequencing Center and Wofford Cain Chair and professor of molecular and human genetics at Baylor. “The GREGoR program has advanced this cause enormously.”
GREGoR has studied thousands of challenging rare disease cases and collected genomic data on approximately 7,500 patients and 3,000 families. Despite major progress, there is still a long way to go. Researchers estimate that more than 10,000 relationships between disease and protein-coding genes still are undiscovered.
“As a field, we are working toward finishing the job of discovering all the novel disease genes,” said co-corresponding author Moez Dawood, graduate student in the Medical Scientist Training Program at Baylor. “New technologies and diagnostic approaches are going to drive clinical discovery.”
Understanding gene regulation better
Part of finishing the job includes unlocking the noncoding genome, the part of the genome that regulates the expression of other genes. GREGoR established a framework for using short-read genome sequencing and long-read sequencing and many of the newest innovations in next generation sequencing and analyses. The consortium has published multiple papers evaluating the utility of these methods in increasing diagnostic yield.
Data sharing
Accelerating data sharing will be a key aspect of advancing the field. All data from the consortium is publicly available to researchers. “We’re hoping people use this data as positive controls to test new tools for rare disease analysis,” Dawood said. “There’s also a bunch of data from patients with unsolved cases. We hope people will bring their new tools and ideas to try to solve these cases as well.”
Read more about the work of GREGoR and major advances in the field of genomics in Nature.
Dr. Stephen B. Montgomery, professor of pathology, genetics and biomedical data science at Stanford University, is co-corresponding author of the publication. Other co-authors affiliated with Baylor College of Medicine include Drs. James R. Lupski, Fritz J. Sedlazeck and Jennifer E. Posey. See the publication for a full list of authors and funding sources.
By Molly Chiu
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