# Discovery and characterization of ocular regulatory elements through evolutionary analysis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $469,263

## Abstract

Project Summary
Eye development is governed by complicated networks of gene regulatory elements, but the field has not
yet characterized or even identified most of the regulatory sequences involved. This project will use new
comparative genomics approaches to reveal hundreds of regulatory regions in the genome crucial to eye
development and function. The project first aims to precisely identify chromosomal regions that are
conserved in sighted species’ genomes but lost or deteriorating in six blind species with regressed eye
structures. Those blind species are 3 unrelated species with the common name “mole”, 2 unrelated “mole-
rats”, and a blind river dolphin. This aim will be achieved using powerful RERconverge software
developed in the Clark and Chikina labs that exploits the phenomenon of convergent evolution to discover
genomic regions unique to species sharing a trait, in this case, blindness. Top-scoring regions will then
be assayed for expression in the eye and other tissues in a zebrafish model of embryonic development
using their sequences from mouse. The second aim will determine the functional consequences of
sequence evolution in species with regressed eyesight. To this end, sequences from blind species will
be contrasted with sequences from their sighted ancestor using experimental characterization of
embryonic expression and genome-wide patterns of open chromatin, as well as through recently
introduced computational models. By studying the sequence changes in blind species, specific
subsequences important for ocular expression will be identified. In the third aim, the project will determine
if these new ocular regions are responsible for congenital eye diseases in human patients. Patients for
whom no causal mutation was found will be sequenced at thousands of conserved, non-coding regions
that surfaced from our evolutionary and functional analyses for eye function. Since causal mutations are
not identified in a majority of cases for most eye diseases, associations between disease and these newly
discovered ocular regulatory regions would explain this deficit and allow more comprehensive diagnosis
in the clinic. Furthermore, eye regulatory regions identified in this project will provide the field of gene
therapy with new sequences and expression patterns to design safer and more precise therapies. Thus,
this project directly addresses the mission of the National Eye Institute by providing avenues to better
diagnosis and treatment of genetic eye diseases.

## Key facts

- **NIH application ID:** 10242928
- **Project number:** 5R01EY030546-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Maria D Chikina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $469,263
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242928

## Citation

> US National Institutes of Health, RePORTER application 10242928, Discovery and characterization of ocular regulatory elements through evolutionary analysis (5R01EY030546-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242928. Licensed CC0.

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