About Us

The vision of the BCM-GREGoR research program is to translate genomic discovery and functional phenotyping to precision molecular diagnosis in the clinic whilst advancing genomics and human genetics research. We seek to advance understanding of gene function through definition of all Mendelian disease traits and cataloging of the phenotypic impact of variant alleles across all ~20,000 protein coding genes. Clinicians and diagnostic laboratories will be invaluable partners as we strive to drive this new knowledge to the “front lines” of healthcare.

Award U01HG011758

Jennifer E Posey, MD, PhD, FACMG - Principal Investigator
Richard A Gibbs, AC, PhD - Principal Investigator
James R. Lupski, MD, PhD, DSc (hon), FAAP, FACMG, FANA, FAAAS, FAAS - Principal Investigator
 

The Broad Institute focuses on improving diagnosis and Mendelian gene discovery through large scale sequencing, methods development, and data sharing. Phenotype areas of high interest include but are not limited to orphan/syndromic, neurodevelopmental, and neuromuscular disorders which come to our center through US and international collaborations with research or clinical groups or through direct to patient recruitment within the US through the Rare Genomes Project. Our approach includes trio exome sequencing, and deeper investigation of exome negative cases with RNAseq, short and long read genome sequencing, application of methods for improved variant detection, CRISPR cell culture models for variants of uncertain significance, data aggregation, and data sharing.

Award U01HG011755

Anne O’Donnell-Luria, MD, PhD - Principal Investigator
Heidi Rehm, PhD - Principal Investigator
Michael Talkowski, PhD - Principal Investigator

To accelerate the pace of Mendelian disease gene discovery and clinical implementation, we propose a Pediatric Mendelian Genomics Research Center (MGRC), leveraging the broad pediatric clinical and research expertise of Children’s National Hospital and Research Institute in a partnership with Invitae’s expertise in providing comprehensive and affordable genetic testing. Our Center will unite world class experts combining basic and translational research with innovative approaches to phenotyping, variant identification and functional investigation of both coding and non-coding sequence changes with the goals of discovering novel Mendelian gene variations and identifying variants not detected on current sequencing pipelines, disambiguating uncertain variants into disease-causing versus benign categorizations, and sharing information by working collaboratively with the MGRC community.

Award U01HG011745

Eric Vilain, MD, PhD - Principal Investigator
Vincent Fusaro, PhD - Co-Investigator

Our goal is to provide a platform for functional genomics research and validation to improve diagnosis in Mendelian disease. We believe that the systematic application of promising new genomics technologies coupled with innovative computational approaches will foster discovery. Research participants who remain undiagnosed after exome sequencing will undergo short read and long read genome sequencing, transcriptome sequencing, methylation assays, metabolomics and/or lipidomics assays. Novel causal variants and genes will be validated through state-of-the-art targeted approaches including massively parallel reporter assays, induced-pluripotent stem cell assays and CRISPR engineered cellular and mouse models. Our approach will help elucidate the most effective ‘omics’ strategies to improve Mendelian disease discovery and diagnosis.

Award U01HG011762

Stephen Montgomery, PhD - Principal Investigator
Matthew Wheeler, MD, PhD - Principal Investigator
Jonathan Bernstein, MD, PhD - Principal Investigator

Mendelian conditions are rare disorders caused by sequence changes of the genome. While genes underlying thousands of Mendelian conditions have been identified, there are thousands of Mendelian conditions for which the gene(s) and sequence changes have yet to be discovered. The UW-CRDR collaborates with an extensive network of clinicians and investigators worldwide and applies cutting edge technologies including next generation sequencing, new analytical tools, and data-sharing innovations to discover new sequence changes and gene(s) that underlie Mendelian conditions. Understanding the genetic basis of Mendelian conditions provides the most efficient way to understand the function of the human genome, enables clinical diagnosis of rare disorders, and represents the keystone of the foundation of precision medicine.

Award U01HG011744

Deborah A. Nickerson, PhD - Principal Investigator
Michael J. Bamshad, MD - Principal Investigator
Evan E. Eichler, PhD - Principal Investigator