# Culling the human genome of disease variants using ultraconserved elements

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $1,049,646

## Abstract

Project Summary/Abstract
Culling the human genome of disease variants using ultraconserved elements
Objectives: The immediate goal of the proposed studies is to explore the process by which a very
curious set of sequences, called ultraconserved elements (UCEs), appear to recognize deleterious ge-
nome rearrangements and then induce cells that carry such rearrangements to cull themselves away.
As such, UCEs may embody an activity that could ultimately enable strategies for clearing bodies of
diseased cells. Given that genome rearrangements lie at the heart of many diseases, including cancers
and neurodevelopmental disorders, the proposed studies have the potential to contribute to the treat-
ment of such diseases. Finally, as UCEs remain one of the least understood sequences of the genome,
the studies proposed here may also contribute to elucidating the structural and functional aspects of
these very enigmatic elements.
 Health relatedness: The proposed studies will pertain to cancer biology, neurodevelopmental dis-
orders, and potentially any disease associated with genome instability, as they stem from a stunningly
nonrandom change in the positional relationship between UCEs and the breakpoints of structural vari-
ants representing healthy individuals and those representing individuals bearing deleterious genome re-
arrangements.
 Innovation: The proposed studies offer two levels of innovation. First, they suggest that UCEs
may constitute a new kind of genetic element, whose function is simply to resist change. This would be
in contrast promoters, enhancers, and transcription units, whose functions are to produce an activity or
a product. The long-term innovation of the proposed studies lies with the notion that UCEs may embody
an endogenous activity which permits cells to assess their genome for deleterious rearrangements and,
thus, may ultimately be harnessed as an exquisitely sensitive surveillance system for protecting our
bodies against disease.
 Specific Aims: The goal of the proposed studies is to explore the potential of using UCEs to clear
cell populations and, thus, bodies of deleterious rearrangements. As such, the proposed aims will use
computational, genetic, molecular genetic, and imaging technologies to:
A. Determine whether UCEs represent a new kind of genetic element.
B. Clarify why UCEs appear so responsive to structural variation.
C. Screen the genome for genes that underlie the responsiveness of UCEs to structural variation.

## Key facts

- **NIH application ID:** 9939592
- **Project number:** 5R01HD091797-05
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** CHAO-TING WU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,049,646
- **Award type:** 5
- **Project period:** 2016-09-19 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939592

## Citation

> US National Institutes of Health, RePORTER application 9939592, Culling the human genome of disease variants using ultraconserved elements (5R01HD091797-05). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/9939592. Licensed CC0.

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