# Unbiased identification and characterization of mouse metastable epialleles

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $500,075

## Abstract

PROJECT SUMMARY (Abstract)
In addition to genetics and environment, interindividual variation in epigenetic regulation may determine risk of
obesity. Exceptional genomic loci called metastable epialleles offer unprecedented opportunities to test this.
Metastable epialleles – essentially epigenetic polymorphisms – exhibit interindividual variation in DNA
methylation that is neither tissue-specific nor genetically mediated. Metastable epialleles were first discovered
in mice when dramatic phenotypic variation was observed amongst inbred mice. Over the last 10 years we
pioneered the discovery and characterization of human metastable epialleles. We have shown that DNA
methylation profiling of multiple tissues in multiple individuals is an effective approach to identifying regions that
exhibit systemic interindividual variation in DNA methylation, a hallmark of metastable epialleles. Now that we
know epigenetic metastability is common to mice and humans, it is essential to identify and explore the full
range of MEs in the mouse. We therefore propose to pursue the following Specific Aims: Aim 1 - Perform an
unbiased screen for mouse metastable epialleles. Aim 2 - Test for effects of maternal dietary methyl donor
supplementation on offspring DNA methylation at metastable epialleles. Aim 3: Use comparative genomics to
identify sequence determinants of epigenetic metastability. Successful completion of these Aims will provide
the foundation for development of mouse (and potentially other mammalian) models which will enable
controlled experiments to help understand how interindividual variation in DNA methylation affects risk of
disease in humans.

## Key facts

- **NIH application ID:** 10032890
- **Project number:** 1R01DK125562-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ROBERT A WATERLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $500,075
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10032890

## Citation

> US National Institutes of Health, RePORTER application 10032890, Unbiased identification and characterization of mouse metastable epialleles (1R01DK125562-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10032890. Licensed CC0.

---

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