# Functional analysis of histone modifier Autism Spectrum Disorders risk genes in vertebrate development

> **NIH NIH K99** · YALE UNIVERSITY · 2022 · $119,308

## Abstract

PROJECT SUMMARY
 Autism Spectrum Disorders (ASD) are a class of developmental disorders characterized by significant social,
communication, and behavioral challenges. ASD is thought to result from neural cell type imbalance during
early development, partly from the discovery of histone modifiers and chromatin regulators as ASD risk genes.
Unfortunately, the cellular, molecular, behavioral, and developmental mechanisms of these ASD risk genes are
not well known. This is underscored by the wide variation in type and severity of symptoms. Systematic
dissection of the roles of candidate histone modifier ASD risk genes is therefore fundamental to understanding
how mutations in these genes leads to cell type imbalances and altered behaviors.
 Recently, our lab has taken advantage of the fast-developing vertebrate system zebrafish, in which histone
modifier genes are highly conserved, to identify behavioral and developmental phenotypes in mutants of
candidate risk genes. Mutants in one of these genes, the lysine methyltransferase kmt2a/mll1, display severe
nighttime hyperactivity and altered cell type specification in the brain. The full developmental and behavioral
phenotypes, or the cell types and circuits/pathways that are affected in these mutants, remain unknown. The
proposed study will combine behavioral and developmental assays, brain activity assays, and single-cell
transcriptomic and chromatin accessibility profiling to directly test the hypothesis that kmt2a functions to
specify cell types required for appropriate nighttime activity behavioral responses during development.
Altogether, findings from this study will uncover unique functional roles and mechanisms for conserved
candidate histone modifier ASD risk genes during early development.

## Key facts

- **NIH application ID:** 10371323
- **Project number:** 1K99HD105001-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Valerie Angela Tornini
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $119,308
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371323

## Citation

> US National Institutes of Health, RePORTER application 10371323, Functional analysis of histone modifier Autism Spectrum Disorders risk genes in vertebrate development (1K99HD105001-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371323. Licensed CC0.

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