# Neurobiology of Autism With Macrocephaly

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $373,118

## Abstract

Major goals of the parent application (R01 MH109648-04, entitled “Neurobiology of Autism with
Macrocephaly) are to investigate developmental alterations in ASD with large brain size
(macrocephaly) and normal brain size (normocephaly) in order to understand whether these
represent biologically distinct subtypes of ASD. To this end, we are collecting and analyzing
neurobiological measures, transcriptome and gene regulatory element (enhancers) activities in
induced pluripotent stem cell (iPSC)- derived organoids obtained from ASD patients with
macrocephaly or normocephaly. Differential gene expression and network analyses in an initial
set of macrocephalic and normocephalic proband-control pairs suggest that more than 75% of
differentially expressed genes between probands and their unaffected fathers were specific to
the macrocephalic or normocephalic groups, confirming our hypothesis that these represent
different subtypes of ASD, and validating our approach to separately analyze these sets of
families and compare their neurobiology. However, power analysis indicate that, in order to
discover 90% of the predicted total number of enhancer elements active in our model, we need
to analyze primary datasets from 10 additional macrocephalic and 7 additional normocephalic
proband-control pairs. For macrocephalic individuals, 8 families are already available, requiring
the recruitment of only 2 additional families. For normocephalic families, all 7 need to be newly
enrolled. All together, under the auspices of this supplement we will recruit 9 families (18
subjects), generate iPSC lines, and produce transcriptome and enhancer datasets. Thus, this
supplement application requests funds to complete recruitment, produce iPSC lines, and
generate primary data which has been halted by the COVID pandemic. Over the years, the
Vaccarino lab has a demonstrated ability to perform this research, as shown by deposition in the
NIMH Stem Cell Resource at Infinity BiologiX LLC of a total of 82 primary cell lines and 121
iPSC lines from families with ASD (NDA collections C1201 and C2424).

## Key facts

- **NIH application ID:** 10358894
- **Project number:** 3R01MH109648-05S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** FLORA M VACCARINO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,118
- **Award type:** 3
- **Project period:** 2021-06-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358894

## Citation

> US National Institutes of Health, RePORTER application 10358894, Neurobiology of Autism With Macrocephaly (3R01MH109648-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10358894. Licensed CC0.

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