Of the RNAs expressed at different levels in the autism brains, 60 are long non-coding RNAs

exosomesfrom Spectrum News by Nicholette Zeliadt

The brains of people with autism show a distinct molecular signature, according to the largest-yet postmortem study of people with the condition1. The signature reflects alterations in how genes are pieced together and expressed.

The findings confirm and extend those from two smaller studies of autism brains — one from 2011 by the same research team and another from 2014 by a different group.

“We can be now fairly certain that this pattern really means something,” says lead researcher Daniel Geschwind, distinguished professor of neurology, psychiatry and human genetics at the University of California, Los Angeles. “However, it goes beyond the convergence,” he adds. “There’s a lot of new biology we’ve learned.”

The study, which appeared 14 December in Nature, suggests that the diverse molecular underpinnings of autism converge on a key set of biological pathways.

“Even with very different genetic and presumably also environmental risk factors that place these people with an autism diagnosis, they all seem to share certain features of their gene expression,” says Evan Macosko, assistant professor of psychiatry at Harvard University, who was not involved in the study. The findings “could give us some deep insight not only potentially into the cause of autism, but also how we might be able to [treat] it.”

Pattern recognition:

Geschwind’s team sequenced RNA in postmortem brain tissue from 48 people with autism and 49 controls. The samples come from either the cerebellum, which coordinates movement, or the frontal and temporal regions of the cerebral cortex, which play key roles in attention, planning and thought.

The researchers identified 584 genes that are expressed at higher levels in the cortical tissue from people with autism than in controls, and 558 expressed at lower levels. This pattern appears in more than two-thirds of the autism samples.

Geschwind’s team found that many of the same genes show altered expression in the cerebellum of people who have autism compared with controls, but the differences are not statistically significant.

Of the RNAs expressed at different levels in the autism brains, 60 are ‘long noncoding RNAs.’ These are RNAs that are not translated into protein but can regulate the expression of other genes. Levels of two of the RNAs — LINC00693 and LINC00689 — normally decrease during development, but are unusually high in autism brains, Geschwind and his team found.

The researchers then looked at gene expression patterns in the frontal and temporal regions of the cortex. They found that the expression of 523 genes differs between the two regions in control brains, but not in the autism brains. This finding could reflect problems in the specialization of these two regions of the cortex in people with autism, Macosko says.

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