OtherMolecular autism2025

Evolutionary constrained genes associated with autism spectrum disorder across 2,054 nonhuman primate genomes.

Yukiko Kikuchi, Mohammed Uddin, Joris A Veltman and 3 others

PMID 39849619

WHAT IT FOUND

Genes linked to autism and other neurodevelopmental disorders in humans are similarly protected from mutation in macaques.

Despite this protection, macaques still carry many predicted damaging variants in these genes, supporting their use as animal models to study the biological roots of these conditions.

Key findings

01Genes associated with autism and other neurodevelopmental disorders in humans show significant evolutionary constraint in macaques, meaning they tolerate fewer mutations than average genes.

02Macaques still harbor predicted damaging mutations in the majority of these constrained neurodevelopmental disorder genes.

03Some key human neurodevelopmental genes are highly constrained in humans but not in macaques, indicating species-specific differences in genetic tolerance.

STILL TO COME

How it was doneWhat they found

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What it does not show

The study lacked behavioral and phenotypic data for the macaques, so it cannot confirm if the genetic variants actually cause symptoms or traits. The gene lists used were very broad, including many genes with weak evidence for causing disorders in humans. The correlation between human and macaque genetic constraint scores was moderate (0.39), suggesting significant species-specific differences in how genes are regulated.

Declared interests

The study was supported by the National Institutes of Health (NIH). No commercial conflicts of interest were reported.

The easy way to misread this

Do not interpret this as evidence that these genetic variants cause autism-like behaviors in macaques. The study found no behavioral data to link the mutations to symptoms, and the specific mutations found in macaques did not match known human autism variants.

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The study

Participants
2,054 macaque genomes
Certainty of evidence
Low

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    Cite

    Yukiko Kikuchi, Mohammed Uddin, Joris A Veltman, et al. Evolutionary constrained genes associated with autism spectrum disorder across 2,054 nonhuman primate genomes. Molecular autism. 2025.

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