# Genetic determinants of early brain development in an animal model of autism spectrum disorder (ASD)

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $243,000

## Abstract

Abstract
The shortened developmental period and similar brain organization make nonhuman primates an ideal model
for studying the exaggerated brain growth hypothesis of autism spectrum disorder (ASD). Specifically,
research indicates that the brain development trajectory is significantly steeper and different in children with
ASD compared to neurotypical controls, and this overgrowth is likely driven by several genes associated with
neurogenesis and synaptic pruning. One such gene is DUF1220, which has been shown to affect brain growth,
but remains largely understudied in the context of intra-individual variability in nonhuman primate brain
development. In adult humans, increased copy number variants in DUF1220 are positively correlated with
individual variation in brain size and brain size pathology. Further, in adult humans, increases in DUF1220
copy number is associated with higher scores on (1) general intelligence, (2) math ability, and (3) increases in
ASD symptom severity. Here, we propose utilizing a nonhuman primate model (rhesus monkeys) to test
whether intra-species increases in DUF1220 copy number is associated with whole and regional brain growth
as well as increased severity of ASD-like behavioral phenotypes. In aim 1, we will quantify copy number
variants in DUF1220 in the 1q21 region (from blood) and acquire in vivo MRI and DTI scans longitudinally in a
sample of 42 monkeys at 6, 12, 18, and 24 months of age. we will perform analyses of variance (ANOVAs)
with DUF1220 copy number in each clade (low/high) and sex (female/male) as the independent variables and
the brain size measures as the dependent variables (total volume, gray and white matter, surface area, cortical
thickness, gyrification, and connectivity). We will also examine the effect of DUF1220 copy number on the
slope of change for our brain measures (across 6, 12, 18, 24 months). In addition, we will use a region-of-
interest approach to quantify gray and white matter within brain regions comprising the social brain network
and test for their association with DUF1220 copy number variants. In aim 2, we plan to assess social cognition
every six months using three cognitive tests selected for their relevance to ASD, including mutual eye gaze
and gaze following, and a social motivation test. We will use ANOVAs to determine the differences in social
motivation, mutual eye gaze, and gaze following between those with low and high DUF1220 copy numbers in
any of the six clades at each time point (6, 12, 18, and 24 months). We will also perform partial correlations to
examine the relationship between gray matter and white matter volumes in the social brain network and scores
on the social cognition tests, with DUF1220 copy number as a covariate. Together these findings will: (1)
provide additional evidence of the utility of nonhuman primate models of ASD, and (2) help elucidate the
developmental time frame for changes in brain size and social cognition, in relation to DUF1220, as ...

## Key facts

- **NIH application ID:** 10215682
- **Project number:** 1R21HD103490-01A1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** WILLIAM D HOPKINS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $243,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215682

## Citation

> US National Institutes of Health, RePORTER application 10215682, Genetic determinants of early brain development in an animal model of autism spectrum disorder (ASD) (1R21HD103490-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10215682. Licensed CC0.

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