# UW Center for Mendelian Genomics

> **NIH NIH UM1** · UNIVERSITY OF WASHINGTON · 2020 · $2,336,727

## Abstract

PROJECT SUMMARY/ABSTRACT (FROM FUNDED PARENT AWARD)
 To date, 2,937 genes underlying 4,163 Mendelian conditions (MCs) have been discovered. However, the
genetic basis of over 3,000 MCs remains unknown, and hundreds of novel MCs are described each year. In
2011, the NHGRI and NHLBI established the Centers for Mendelian Genomics (CMG) to facilitate large-scale
discovery of genes responsible for MCs. In Phase-1 of the CMG program, and in partnership with 182
investigators from 117 institutions in 27 countries, the University of Washington CMG (UW-CMG) assessed
6,598 samples from 2,404 families and has, to date, produced 4,116 exome and 97 whole genome sequences.
This extensive collaborative effort resulted in an unparalleled pace of discovery with the identification of genes
for 237 MCs, including 123 novel discoveries. The translation and impact of these discoveries on diagnostics
and clinical care has been immediate and substantial—when combined with discoveries made by the genetics
community at-large, variants in genes identified as underlying MCs since 2012 represent ~25% of positive
results in clinical diagnostic efforts. Additionally, the UW-CMG has developed multiple new analytical tools
including CADD, PRIMUS, SimRare, STAR, RV-TDT, CHP, VAT and Spliceosaurus as well as methodological
innovations including MIPs, smMIPs and approaches for low input exome and genome sequencing. The UW-
CMG remains deeply committed to open data sharing with rolling submission of eligible exome and genome
data to dbGaP (614 deposited and 1,748 pending deposition) and development of a new data browser
(http://geno2mp.gs.washington.edu) that, for the first time, publicly provides anonymized links between
individual-level genotypes, from over 3,000 exomes, to individual clinical phenotypes, defined by Human
Phenotype Ontology terms. In this renewal application, we build from these successes to maximize novel gene
discovery for MCs, capitalizing on immediate access to >22,000 sequence-ready samples from >16,500
families and 163 MCs, access to several large cohorts of birth defects totaling more than 24,000 trios (>94,000
samples total) and an aggressive sample solicitation plan including case aggregation and case matching of
undiagnosed patients who have undergone clinical exome sequencing. We propose four specific aims: (1)
Solicit, organize, and curate phenotypic information and DNA samples from families with unexplained (i.e., no
known underlying gene) MCs from sample custodians around the world, by submission to our center of either
samples for sequencing or sequence data for further analysis; (2) Apply our established production pipeline for
exome and genome sequencing to samples corresponding to unexplained MCs and to improve this process
through ongoing technology innovation; (3) Determine the genetic basis of as many unexplained MCs as is
possible, maximizing novel discovery, by use of efficient study design and effective, innovative analysis; (4)
Take a lea...

## Key facts

- **NIH application ID:** 9922590
- **Project number:** 3UM1HG006493-08S2
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** MICHAEL Joseph BAMSHAD
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,336,727
- **Award type:** 3
- **Project period:** 2019-04-29 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922590

## Citation

> US National Institutes of Health, RePORTER application 9922590, UW Center for Mendelian Genomics (3UM1HG006493-08S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9922590. Licensed CC0.

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