# The evolution of genomic imprinting

> **NIH NIH R01** · UNIVERSITY OF MONTANA · 2020 · $293,712

## Abstract

Genomic imprinting is a form of epigenetic gene regulation that plays a key role in placental
development. Imprinted expression is highly enriched within developmental pathways and, as a
consequence, the disruption of imprinted pathways results in a range of congenital
developmental disorders in humans and other mammals. Mammalian hybrids often manifest
many of the same placental growth abnormalities, raising the intriguing possibility that recurrent
developmental syndromes within and between species may reflect the disruption of common
regulatory pathways. However, surprisingly little is known about the evolution of imprinted
regulatory networks, and the contribution of disrupted genomic imprinting to the evolution of
reproductive barriers between species remains unresolved. The proposed research will begin to
overcome these fundamental gaps in knowledge by generating novel comparative genomic data
on placental gene expression and genomic imprinting among closely related species and their
reciprocal hybrids. Specific Aims 1 and 2 will use a series of hybrid rodent systems to generate
an atlas of genome-wide placental transcription, DNA methylation, and chromatin structure
across five species and two major lineages of rodents (house mice and dwarf hamsters). These
unprecedented comparative data will allow us to resolve the basic epigenetic mechanisms
controlling genomic imprinting and quantify how placental expression and imprinting has
evolved over 30 million years of divergence. Specific Aim 3 will use a systems genetics
approach to examine the genetic architecture of hybrid overgrowth, placental expression, and
imprinting in dwarf hamsters and mice. These experiments will allow us to understand the
mechanistic and genetic underpinnings of a common form of placental dysplasia and test the
novel hypothesis the X chromosome plays a central role in the regulation of imprinted autosomal
regulatory networks. The long-term goals of this research program are to (1) illuminate the basic
epigenetic mechanisms controlling genomic imprinting, (2) provide insights into the evolutionary
tempo and theoretical drivers of imprinting and other aspects of placental expression, (3) test
hypotheses on the causal connection between disrupted imprinting and abnormal placental
development, (4) understand the organization and evolution of imprinted expression networks,
and (5) link these conceptual advances to understand the contribution of genomic imprinting to
the origin of biological diversity.

## Key facts

- **NIH application ID:** 9840836
- **Project number:** 5R01HD094787-03
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Jeffrey Good
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,712
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840836

## Citation

> US National Institutes of Health, RePORTER application 9840836, The evolution of genomic imprinting (5R01HD094787-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9840836. Licensed CC0.

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