# Elucidating Genotype-Phenotype Relationship of Polygenic Dilated Cardiomyopathies: Administrative Supplement (INCLUDE)

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $501,316

## Abstract

PROJECT SUMMARY
Down syndrome (DS) is the most common chromosomal abnormality affecting one in every 700 live births. Up
to 50% of individuals born with DS, also known as trisomy 21 (T21), are born with a congenital heart disease
(CHD). Despite the high frequency of DS-CHD, the exact mechanisms of DS-related CHD remain unknown. In
this Supplement to the Parent R01 HL130020-5, we propose to leverage our established iPSC-based
experimental models to understand the genetic basis of DS-CHD. We hypothesize that an interaction of genes
between T21 and non-T21 mutations causes CHD in DS. Patients. In Aim 1, we will perform whole genome-
sequencing (WGS) in DS patients with or without CHD to identify single nucleotide variants (SNV) associated
with DS-CHD. In Aim 2, we will validate the pathogenicity of SNVs on development of CHDs in the presence of
T21. We will use CRISPR/Cas9 to correct or insert the SNVs to iPSCs from control and DS patients to establish
a genotype-phenotype relationship between SNVs and CHDs. Completing the aims of this supplement will likely
increase our understanding of DS-related CHD as well as broaden the overall impact of the parent R01 award.
In summary, this INCLUDE Administrative Supplement proposal will create novel opportunities to build a massive
functional and sequencing database as well as iPSC biorepository that will be broadly shared with multi-
disciplinary investigators. The combination of deep clinical phenotyping, the use of iPSC, CRISPR/Cas9 and
multi-omic approaches will undoubtedly help to move this field forward and better understand DS-related cardiac
pathologies.

## Key facts

- **NIH application ID:** 10404723
- **Project number:** 3R01HL130020-06S3
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** THOMAS QUERTERMOUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $501,316
- **Award type:** 3
- **Project period:** 2015-12-16 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404723

## Citation

> US National Institutes of Health, RePORTER application 10404723, Elucidating Genotype-Phenotype Relationship of Polygenic Dilated Cardiomyopathies: Administrative Supplement (INCLUDE) (3R01HL130020-06S3). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10404723. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*