# KOMP2 Administrative Supplement-Using Mouse Essentiality Screen to Identify Disease Genes Causing Severe Human Phenotypes With Early Lethality

> **NIH NIH UM1** · BAYLOR COLLEGE OF MEDICINE · 2020 · $243,331

## Abstract

ABSTRACT
The long-term goal of this project is to determine the cause of birth defects in critically-ill
undiagnosed infants, using the embryonic phenotyping pipeline within the Knockout Mouse
Phenotyping Program (KOMP2), with focus on post-implantation developmental lethality and
sub-viability. Genes in this category are intuitively predicted to be associated with congenital
anomalies, with likely enrichment for dominant disorders. The haplo-essential genes in mice that
cannot go beyond the founder stage are likely enriched for human haploinsufficient genes
responsible for Mendelian diseases and developmental disorders. Through this proposal, the
investigator will prioritize de novo, LoF and other variants in genes with high pLI score from
exome sequencing (ES) studies of the deceased children from her previously published study
(PMID: 28973083). The genes with putative dominant null alleles will then be intersected with
the known developmental essential and subviable genes in the International Mouse
Phenotyping Consortium (IMPC) dataset to find phenotypic correlations. The investigator will
use the embryonic lethal data to particularly analyze undiagnosed human cardiovascular
phenotypes with early lethality. Through this opportunity for career enhancement in genomics,
the applicant who is primarily a clinician, will learn to compare the mouse and human
phenotypes using standardized phenotype terms and to utilize automated tools designed by
IMPC to accelerate discovery of rare diseases. The investigator anticipates acquiring skills and
hands-on experience to evaluate morphological abnormalities in developmental essential
mouse embryos under the supervision of Dr. Dickinson's team. The scope of work, using mouse
embryonic data to find clinical utility for patients with undiagnosed genetic conditions is in
complete alignment with the project goals of KOMP2. The proposed work will also prepare the
investigator to accelerate her existing efforts on rare disease diagnoses in children.

## Key facts

- **NIH application ID:** 10166090
- **Project number:** 3UM1HG006348-10S2
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mary E Dickinson
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,331
- **Award type:** 3
- **Project period:** 2011-09-28 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166090

## Citation

> US National Institutes of Health, RePORTER application 10166090, KOMP2 Administrative Supplement-Using Mouse Essentiality Screen to Identify Disease Genes Causing Severe Human Phenotypes With Early Lethality (3UM1HG006348-10S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166090. Licensed CC0.

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