Consortium Makes Strides in Diagnosing Rare Diseases through Genomics

The National Institutes of Health (NIH) has made significant advancements in the field of rare disease diagnostics through the establishment of the Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium in 2021. This initiative aims to find molecular diagnoses for individuals with rare diseases who remain undiagnosed despite clinical testing. Among the consortium’s five clinical sites is the Baylor College of Medicine, where researchers are focusing on solving the challenges presented by these often elusive conditions.

A recent paper published in the journal Nature highlights the key achievements of the GREGoR Consortium in its first five years. The report also outlines the future directions for genomic medicine that researchers plan to explore. Rare diseases, while individually uncommon, collectively affect approximately one in 20 people worldwide, emphasizing the need for improved diagnostic methods.

Advancements in genomic sequencing, particularly the widespread application of exome sequencing and computational analysis, have led to notable improvements in diagnosing rare diseases. To date, more than 5,000 protein-coding genes have been identified as being implicated in various diseases.

Identifying Genes Linked to Rare Diseases

In discussing the importance of identifying genes associated with rare diseases, Dr. Richard Gibbs, director of the Human Genome Sequencing Center and professor of molecular and human genetics at Baylor, stated, “Identifying the genes underlying rare disease remains the most powerful gateway to the understanding of basic molecular processes in humans. The GREGoR program has advanced this cause enormously.”

Over the past five years, GREGoR has investigated thousands of rare disease cases, collecting genomic data from approximately 7,500 patients and 3,000 families. Despite these advancements, researchers believe there is still much work to be done. They estimate that over 10,000 relationships between diseases and protein-coding genes remain undiscovered. Moez Dawood, a graduate student in the Medical Scientist Training Program at Baylor and co-corresponding author of the recent paper, emphasized, “As a field, we are working toward finishing the job of discovering all the novel disease genes. New technologies and diagnostic approaches are going to drive clinical discovery.”

Unlocking the Noncoding Genome

A crucial part of completing this task involves understanding the noncoding genome, which regulates the expression of other genes. GREGoR has developed a framework that utilizes both short-read and long-read sequencing, along with the latest innovations in next-generation sequencing techniques. The consortium has published multiple papers assessing the effectiveness of these methods in enhancing diagnostic yields.

Accelerating data sharing is another vital aspect of progressing in this field. All data collected by the consortium is publicly accessible to researchers. Dawood noted, “We’re hoping people use this data as positive controls to test new tools for rare disease analysis. 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.”

The ongoing efforts of the GREGoR Consortium represent a significant step forward in the quest to improve diagnostics for rare diseases. As researchers continue to unlock the complexities of the human genome, the potential for new discoveries that could change lives remains vast. For further details, consult the work of Moez Dawood and colleagues in their recent publication titled “GREGoR: accelerating genomics for rare diseases,” available in Nature.