Deep focus: Subcortical brain structures contribute to autism more than previously appreciated, according to two new preprints. One study used single-cell RNA sequencing to identify altered gene expression and found that excitatory neurons in the thalamus and hypothalamus are particularly enriched in autism-linked genes, along with cortical regions. The other study used a different method […]
Hundreds of compounds counteract specific behavioral effects of autism-linked gene variants in zebrafish, according to a new study that, its authors say, could guide precision gene-based medicine for some forms of autism. Many new drugs under investigation for the condition prove ineffective in clinical trials—in part because of its genetic and clinical heterogeneity. “A medication […]
Sleeping flies: Gene variants linked to autism may also give rise to differences n sleep behaviors, according to two new Drosophila studies. In one study, flies with FOXP variants exhibit “severely fragmented and reduced sleep,” in addition to disruptions in circadian rhythms. In the other, a preprint, investigators engineered flies with NLGN3 variants and found […]
Different genetic variants associated with autism converge on common biological processes that shape the developing brain, according to a large study of organoids derived from autistic people’s cells. Individual variants initially alter neurodevelopment in distinct ways, but over time they all disrupt neuron maturation and other key processes, the study shows. Previous work, including postmortem […]
Pulling threads: A new study describes how genetic background can influence neurodevelopmental phenotypes linked to a particular gene variant. To wit, when a parent and child both carry the 16p12.1 deletion, they often experience different clinical presentations. The researchers evaluated 17 classes of secondary variants and identified those that influenced risk for specific traits, such […]
Long-read sequencing reveals novel autism-linked variants that short-read sequencing misses, according to two preprints posted on medRxiv in July. “These are two very nice papers from top labs. They both make compelling cases for long-read sequencing,” says Michael Gandal, associate professor of psychiatry, genetics and pediatrics at the University of Pennsylvania Perelman School of Medicine, […]
A broad swath of neuropsychiatric conditions, including autism, depression and schizophrenia, share genetic underpinnings. But individual variants can have strikingly different effects on clinical diagnoses: A variant that increases the likelihood of one condition may reduce that of another, according to two new preprints. “When you delete and duplicate genes, you get very different, often […]
Kettle of fish: More than two dozen strains of zebrafish with autism-linked gene variants share overlapping developmental pathways that lead to differences in social behavior, brain activity patterns and brain size, according to a new study. Molecular drivers of the differences include altered function in neuropeptide signaling, neuronal maturation and cell proliferation, which the authors […]
Social skills: Tendencies to engage in groom soliciting, solitary play or sitting alone are highly heritable among macaques. Courtesy of Emory University / Marie Collantes Some aspects of rhesus macaques’ social behavior are strongly shaped by genetics, with differences tied to variants in autism-linked genes, according to a new study. The findings may shed light […]
Growth spurt: An autism-linked mutation shifts the balance of excitatory (pink) and inhibitory (green) neurons during development. Mutations in three genes strongly associated with autism shift the pace at which certain inhibitory and excitatory neurons develop, according to a study published today in Nature. The findings reveal a novel point of convergence by which the […]
Pruning: Neurons from mice lacking one copy of ASH1L (third row) do not prune away as many synapses (bottom row) as control neurons (top and second rows) after stimulation. Loss of the autism-related gene ASH1L leads to excess synapses and autism-like behaviors in mice, according to a study published today in Neuron. Increasing the activity […]
In a fix: mice lacking the autism-related gene POGZ have an altered expression of ADNP, which is also associated with autism. The POGZ gene associated with autism, according to a new mouse study, facilitates the accessibility and expression of genes involved in wiring the brain in utero. People with a mutation in POGZ are more […]
