Rare Daily Staff

The National Institutes of Health will award nearly $80 million to support the establishment of the Mendelian Genomics Research Consortium and the development of novel methods and approaches that help researchers identify the genetic causes of single-gene diseases.

More than 400 million people worldwide have been diagnosed with one of about 7,000 Mendelian diseases, which are disorders generally thought to be caused by mutations in a single gene. The awards will be provided by the National Human Genome Research Institute (NHGRI), part of NIH, and are expected to support the consortium over a period of five years. Current methods can identify a mutation in only about 50 percent of people with a rare disease.

“The idea is to look for the missing causes and genome changes that lead to these rare conditions. This has a lot to do with our ability to interpret the impact of rare variation in the genome,” said Deborah Nickerson, professor of genome sciences at the University of Washington School of Medicine and a principal investigator on the new grant. “It’s from rare, impactful differences in our genomes that provide insights into the parts of the genome that are important for structure and function in humans.”

The new Mendelian Genomics Research Consortium will include four clinical sites and one data coordination center. The clinical sites aim to significantly increase the number of known Mendelian disease genes by implementing new genome-sequencing technologies, novel analytical approaches and international data sharing that includes appropriate patient consent. Research teams will also plan outreach and education efforts to empower the broader research community to perform more robust Mendelian gene discovery projects.

The consortium’s goal is to significantly increase the number of Mendelian disorders for which the genetic cause is known. The teams will perform enhanced data sharing and collaboration, and focus on applying new technologies, genome-sequencing strategies, and analytical approaches.

“This consortium goes a significant step beyond NHGRI’s already successful efforts in this area but adds a more intense focus on data sharing and enabling the broader research community to tackle challenging diseases whose genetic causes were eluding identification by researchers,” said Carolyn Hutter, director of the NHGRI Division of Genome Sciences.

Researchers have been identifying about 300 Mendelian disease genes each year using whole-exome sequencing. This method sequences all the regions of the genome responsible for encoding proteins. However, whole-exome sequencing has not been successful in identifying the genes responsible for many Mendelian diseases, requiring new ways of approaching the problem.

The consortium’s work to develop innovative methods to increase the rate at which the genes responsible for all Mendelian diseases can be identified. 

In addition to the University of Washington’s Nickerson, the new clinical centers will be led by Stephen Montgomery at Stanford University School of Medicine, Anne O’Donnell-Luria at the Broad Institute of MIT and Harvard, Eric Vilain at the Center for Genetic Medicine Research at Children’s National Hospital, and Jennifer Posey at the Baylor College of Medicine.

Susanne May at the University of Washington School of Public Health will lead the data coordination center, which will manage the release of genomic data and facilitate data sharing. 

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