Welcome to the Broad Center for Mendelian Genomics, a collaborative community focused on gene discovery.

Our Mission

The goal of the CMG program is to discover new genes that underlie Mendelian diseases. To that end, our Center applies large-scale genomic methods - exome, whole-genome and transcriptome sequencing - to thousands of undiagnosed rare disease families. Our approach to gene discovery is characterized by deep interactions between our informatics team and clinical collaborators, using a secure online analysis platform, seqr, and by rapid and open sharing of resources and data with the wider rare disease community.

Learn about our disease areas of focus

Retinal	Muscle	Neurodevelopmental
Orphan	Cardiac	Kidney

An open source software platform for rare disease genomics

Next Generation Sequencing (NGS) is a powerful diagnostic and research tool for Mendelian disease, but without proper tools, this data can be inaccessible to researchers. We are developing seqr as an open source web interface to make research productive, accessible, and user-friendly while leveraging resources and infrastructure at the Broad Institute.

Stories that inspire us

The first undiagnosed Neuromuscular disease family exome sequenced at the Broad Institute was a family with two affected girls with a recessive form of Nemaline Myopathy. We were able to identify two disruptive mutations in LMOD3. Working with our collaborators at the Institute for Neuroscience and Muscle Research (INMR) we identified 14 families from USA, Finland, Japan and the UK. Additional functional studies including a zebra fish model was able to provide further supporting evidence associating LMOD3 as a novel cause of Nemaline Myopathy. It was very thrilling to end the decade long diagnostic journey for this family!

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The MYOSEQ project was sequenced at the Broad Institute in collaboration with the neuromuscular team at Newcastle University is aimed at the application of whole exome sequencing (WES), in a large cohort of patients with unexplained limb‐girdle weakness (LGW). Focusing on undiagnosed patients across clinical centers in Europe and the Middle East with clearly defined clinical phenotypes enables increased diagnostic rates for known genes in particular Pompe disease, GNE related pathologies and other known Limb Girdle Muscular Dystrophy (LGMD) subtypes in this cohort, while the use of WES provides scope both for new gene discovery and for additional research into disease modifiers and genotype‐phenotype correlation with substantial cost effectiveness. To date we have sequenced and analyzed over 1000 LGMD patients.

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Using exome sequencing we were able to identify BICD2 as a novel cause of a dominant form of spinal muscular atrophy (SMA) in an affected boy. Prior to the availability of exome sequencing, 6 candidate linkage regions were identified but it was not practical to screen each gene in these regions beyond ruling out known SMA genes. We were able to identify 5 other families from Austria, Germany and the UK. Two other groups independently published this discovery in the same issue of American Journal of Human Genetics.

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Join the community

Learn more about the researchers, clinicians, and partners working to improve Mendelian Disease gene discovery.