# University of Washington Mendelian Genomics Research Center (UW-MGRC)

> **NIH NIH U01** · UNIVERSITY OF WASHINGTON · 2022 · $2,697,606

## Abstract

PROJECT SUMMARY/ABSTRACT
The genetic basis of >2,920 Mendelian conditions (MCs) remains unknown, and hundreds of novel MCs are
described each year. Our group has, in partnership with 2,379 investigators from 656 institutions in 55 countries,
assessed 15,387 samples from 5,675 families and has, over the past decade, identified genes for 1379 MCs,
including 915 novel discoveries. The translation and impact of these discoveries on diagnostics and clinical care
has been immediate and substantial. Additionally, we have developed multiple new analytical tools including
CADD, PRIMUS, CoNIFER, SMRT-SV, RV-TDT, as well as methodological innovations including MIPs, smMIPs,
and approaches for low input exome and genome sequencing (ES/WGS). We are also deeply committed to open
data sharing with rolling submission of exome and genome data to the AnVIL (1,439 deposited); development of
a MatchMaker Exchange node (http://MyGene2.org) that enables public sharing of genotype and phenotypic
data among families, researchers, and clinicians; and creation of a public data browser
(http://geno2mp.gs.washington.edu) that links de-identified, individual-level genotypes from over 18,000
exomes/genomes to individual phenotypes. In this application, we build upon these successes to establish the
University of Washington Mendelian Genomics Research Center (UW-MGRC) with the overarching goal to
maximize novel gene discovery for MCs, with an emphasis on canonical MCs that have gone unsolved using
ES/WGS, and noncoding variants underlying MCs. To this end, we will develop novel approaches to inform
variant interpretation and functional validation for the human genetics community at-large and disseminate
results, data, and tools openly. We will capitalize on immediate access to sequence-ready samples from ~300
MCs (>26,000 samples), 1,500 samples suspected of harboring a causal noncoding variant for a MC, and an
aggressive sample solicitation plan in partnership with industry, academic centers, and other NIH programs. We
propose three specific aims: (1) maximize novel gene discovery for MCs by solicitation, sequencing, and analysis
of families with unexplained (i.e., no known underlying gene) MCs; classic MCs considered high priority by the
clinical genetics community and that have been recalcitrant to gene discovery efforts; and cases that remain
unsolved after prior exome or genome sequencing. (2) Develop new strategies for gene discovery for unsolved
MCs caused by variants that are difficult to detect or of unknown functional effects (e.g., structural variants,
repeat expansions, cryptic splice, regulatory, etc.), and/or unusual modes of inheritance, and, in doing so,
characterize the genetic architecture of pathogenic noncoding variants underlying MCs. Implement high-
throughput screening and targeted follow-up functional studies to prioritize and validate assertions of
pathogenicity of candidate noncoding variants. (3) Take a leadership role to openly and publicly, when fe...

## Key facts

- **NIH application ID:** 10415070
- **Project number:** 5U01HG011744-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** MICHAEL Joseph BAMSHAD
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,697,606
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415070

## Citation

> US National Institutes of Health, RePORTER application 10415070, University of Washington Mendelian Genomics Research Center (UW-MGRC) (5U01HG011744-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10415070. Licensed CC0.

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