# Joint Center for Mendelian Genomics

> **NIH NIH UM1** · BROAD INSTITUTE, INC. · 2020 · $2,885,036

## Abstract

Abstract
Despite recent advances in genomic technology, more than half of the genes underlying severe Mendelian
disease remain undiscovered. Identifying the genes responsible for rare diseases can yield critical new insights
into human biology, empowering the development of therapies for these diseases as well as more common
conditions. However, current approaches are inadequate to detect or correctly interpret many of the variants
likely to cause rare diseases. Assembling a complete catalogue of genes that underlie rare diseases will
require fundamentally new approaches to gene discovery and variant interpretation. The Joint Center for
Mendelian Genomics, led by the Broad Institute, Boston Children's Hospital, and Rockefeller University, has
assembled a large, international network of collaborators with a world-class track record of both genomic
methods development and Mendelian gene discovery. Our Center's global team of clinical investigators has
both strong domain expertise and access to wider collaborative networks, providing over 35,000 existing well-
phenotyped samples from over 16,000 Mendelian families for genomic analysis as well as strong sources of
ongoing and diverse recruitment. We will apply deep, high-quality exome sequencing, analyzing over 10,000
exomes, to systematically discover causal variants in or near protein-coding regions. Secondly, we will use
PCR-free whole-genome sequencing and novel variant- calling methods for comprehensive discovery in 7,000
samples from exome-unsolved families. Finally, we will apply transcriptome sequencing of disease-relevant
tissues and cell lines from Mendelian patients to focus the search for variants altering gene expression or
transcript splicing. We will implement a robust analytical framework for variant assessment and disease gene
discovery, taking advantage of our investigators' world-leading roles in statistical genetics, functional
annotation, and clinical variant interpretation, as well as access to exome and genome data from over 250,000
reference samples, to build a systematic pipeline for Mendelian gene discovery applied across all patients
sequenced by the Center, and also made freely available to external investigators. For many rare diseases,
confident discovery of causal genes will require aggregation of cases across centers around the world. To
enable this, we will set a new standard for data sharing in clinical genomics by rapidly releasing genetic and
phenotype data to an international network of databases, accelerating collaboration and facilitating robust
disease gene discovery.

## Key facts

- **NIH application ID:** 9923410
- **Project number:** 3UM1HG008900-04S1
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Anne O'Donnell-Luria
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,885,036
- **Award type:** 3
- **Project period:** 2016-01-14 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923410

## Citation

> US National Institutes of Health, RePORTER application 9923410, Joint Center for Mendelian Genomics (3UM1HG008900-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9923410. Licensed CC0.

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