Overview
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The Center for Mendelian Genomics is a member of the GREGoR Consortium (Genomics Research to Elucidate the Genetics of Rare Disease) funded by the NHGRI (National Human Genome Research Institute), along with 5 other sites across the country.
The central goals of the GREGoR consortium are: to discover variants and genes underlying Mendelian diseases; to collaboratively facilitate gene discovery, validation and follow up; and to generate new methods for improving diagnosis across a wide spectrum of rare disorders.
Benefits
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Cost
The Broad CMG provides research sequencing for families affected by Mendelian diseases.
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seqr
Through our Broad-developed seqr software, we will provide an online portal allowing collaborators the ability to analyze their own data, alongside the Broad’s reference. Click here to access seqr.
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Connection to Others
The Broad CMG will also support generation of manuscripts reporting novel genes by providing publication-quality text and figures, connecting collaborators with sources of additional cases with mutations in the same gene, and creating a network of investigators capable of functional validation of newly discovered genes.
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High Quality Sequencing
Samples are sequenced at the Broad Institute’s Genomics Platform, which produces high quality data.
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Variant Calling
GREGoR samples sequenced at the Broad will be jointly called using our best-in-class GATK variant calling pipeline.
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Analysis
Our analysts will work closely with collaborators in exploring the data and providing candidate and likely casual variants, and will work in tandem with your team to discuss challenging cases.
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Disease Areas of Focus
We emphasize recruitment of cases from three major disease areas: neuromuscular, neurodevelopmental, and orphan/syndromic disease- but we consider cases from other disease areas.
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Orphan
A rare, or “orphan” disease is defined as a disease or disorder that affects less than 200,000 people in the United States at any given time. However, there are approximately 30 million people in the U.S. that are affected by a rare disease. We will recruit samples from patients with rare, undiagnosed diseases with a suspected Mendelian basis.
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Muscle
Inherited neuromuscular diseases represent diverse clinical phenotypes with the unifying feature of weakness; primary muscle disease alone has a combined population prevalence of over one in 3,000. Currently over 50% of neuromuscular disease patients cannot be provided with a genetic diagnosis even after extensive targeted screening of known genes, indicating that many causal genes remain undiscovered.
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Neurodev
Neurodevelopmental disorders (NDDs) affect ~4-6% of the population and account for >5-10% of total healthcare costs. Mendelian NDDs remain a diagnostic dilemma because they are frequently difficult to distinguish from NDDs with more complex inheritance, like autism or epilepsy. Collectively NDDs comprise the biggest set of discoveries of Mendelian centers to date, but more than 50% of patients are still left undiagnosed, indicating that NDDs remain a fertile area for novel gene discovery. To enrich for new genes, we will focus primarily on cases with specific features (e.g. metabolic, degenerative, ataxia, microcephaly, syndromic) for which Mendelian causes far outweigh non-Mendelian ones.