# Unraveling correlations between Mendelian and common disease using functional genomics

> **NIH NIH DP5** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $390,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Individualized diagnosis and treatment based on the integration of clinical, genomic, epigenetic and other
biomarkers represent the promise of precision medicine. While most precision medicine initiatives are geared
towards cancer treatment and common disease, which affect more than 5% of the population, this proposal
seeks to bring the goals of precision medicine to those affected by rare Mendelian genetic diseases. The goal
of my research group is to unravel the relationships between Mendelian and common disease through the lens
of rare Mendelian syndromes. Our overarching approach will integrate multiple functional genomic studies
(RNA-seq and ChIP-seq) from patients with rare Mendelian syndromes to publically available genome wide
association study (GWAS) data. Using these data, we will achieve the parallel objectives of 1) revealing the
underlying biological mechanisms of rare disease and 2) their intersection with genetic loci associated with
common diseases. We will focus our study on the novel genetic syndrome of global developmental delay that
we first identified as caused by de novo mutations in KAT6A (Lysine (K) acetyltransferase 6A). KAT6A belongs
to a family of acetyltransferase genes and one of its main functions is to modify histones and control the
expression of a wide set of downstream genes. In Aim 1, we will identify KAT6A target genes using patient-
derived dermal fibroblast cell lines and generate functional genomic data such as RNA-seq and ChIP-seq.
These data will be integrated to identify high priority target genes and functionally validated in human cell lines.
Aim 2 will address the hypothesis that Mendelian disease mutations affect expression of genes underlying
common disease (i.e. autoimmune disease, autism) thereby altering the risk of common disease.
Neurocognitive, behavioral and developmental phenotyping will be performed to quantify co-existing common
disease phenotypes and will be integrated with individual functional genomic data and disease-specific GWAS.
Findings from these studies will advance our ability to interpret the influence of Mendelian gene mutations on
common disease loci within a single individual, thus providing a critical link between Mendelian and common
disease. In doing so, we will advance precision medicine approaches with respect to Mendelian disease, with
the ultimate goal of identifying rational gene targets to use in identification of future therapies for these rare
conditions.

## Key facts

- **NIH application ID:** 10247564
- **Project number:** 5DP5OD024579-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Valerie A Arboleda
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247564

## Citation

> US National Institutes of Health, RePORTER application 10247564, Unraveling correlations between Mendelian and common disease using functional genomics (5DP5OD024579-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247564. Licensed CC0.

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