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The Tufts Daily
Where you read it first | Wednesday, June 12, 2024

A Taste of Tufts: Monaco discusses genetics behind autism, other neurodevelopmental disorders


University President Anthony Monaco's duties may now include courting university donors and sledding down the President's Lawn, but before coming to the Hill the Delaware native began nearly two decades across the pond working on something a little more scientific - studying the genetic basis of neurodevelopmental disorders, including autism and dyslexia.

Monaco presented his research in a reprised role at the weekly Experimental College "Taste of Tufts" lecture Friday, explaining to an audience the research he has conducted over the past 19 years.

"The premise behind this was to bring together a number of different disciplines - so computer [scientists] and mathematicians ... statisticians, alongside geneticists, alongside structural biologists and molecular and cell biologists - to work on the biological basis of [common] disorders," Monaco said at the talk. "The genetics community had shown that we could identify genes for monogenic disorders, but could we use some of the same principles to identify genes that are not absolutely mutated in a ... complex disorder, increase susceptibility to that disorder? We knew that there would be a large number of genes [in] many of these different diseases."

Monaco discussed the influence environment can have on why neurodevelopmental disorder clusters may appear in a family.

"You measure how many times you see [the disorder]," he said. "If it's much higher,
[one can say] that's because the family shares genes and therefore [there] must be genetic susceptibility to these disorders, but we know that families also share their environment." 

Long-term studies on twins can help researchers measure whether a disorder is caused by heritable factors or environmental ones.

"Hopefully we can control for the environment because they're sharing the same environment," he said. Monaco said he and his fellow researchers found that the neurodevelopmental disorders they were studying "have a very strong genetic component," and were primarily caused by chromosomal translocations and copy number variants. A copy number variant is the deletion or duplication of base pairs in a chromosome, and can often be carried in an individual that does not actually have the disease.

According to Monaco, copy number variants have become very important in studying the biological basis of autism, a neurodevelopmental disorder originally diagnosed by Leo Kanner in the 1940s. Individuals with autism are identified as having impairments in communication and social skills.

"If the mother comes in the room, most children look up [and] want to interact with their mother or father," Monaco said. "Children with autism will typically continue to just play with their toy and act like the person's not even there. They also like very repetitive and [stereotypical] patterns and interests, they like to play with the same toy every day."

Although Monaco and his colleagues in the scientific community have been able to identify some genes that contribute to autism, they have found that there is no single direct cause.

"So it's like having a huge jigsaw puzzle, and every time you identify a gene you put one piece into place," he said. "It's not until you can really identify a large number of these genes [that] we can get a picture of what's actually going on."

A goal of this research would be to catch autism early on in a child by searching for certain mutations in their genes.

"The onset is usually four [or] three years old, and it does persist throughout life, although there's a lot of variance in that it's quite frequent in the population and seems to have been increasing over the last couple decades," Monaco said. "And like all neurodevelopmental disorders, males seem more susceptible than females."

Monaco pointed out, though, that beyond the current scientific limitations in uncovering more about the genes, there are also certain ethical issues involved with autism diagnosis.

"If you have a younger sibling of a child who's diagnosed with autism - you find the mutation in the older child - and then you test the younger child, what does that mean for that child if you find the mutation?" Monaco said. "They may never go on to develop autism and you've now stigmatized them as carrying the same mutation as their affected brother or sister."

Monaco also discussed his research on SLI, another neurodevelopmental disorder that is expressed in multiple ways. Individuals with SLI may have difficulty with a wide range of language-related skills. They may also have verbal dyspraxia, or difficulty with movements of the mouth and face required for speech.

Additionally, affected individuals may have an increased risk of psychoses, but their non-verbal skills will be unaffected by the disorder. In discussing SLI and dyslexia, Monaco also clarified confusions surrounding FOXP2 gene and its role in those disorders.

"[FOXP2] is not the gene for speech. Yes, we identified this gene in a family that has a speech and language disorder, but as I described for you  . . . genes are not prescriptive for certain types of illnesses," Monaco said.

Though popular belief has pinpointed the FOXP2 gene as the factor separating humans from other animals that lack speech, Monaco noted that a conservative FOXP2 gene can be found in mice and birds for squeaks and songs, respectively.

In his brief discussion of dyslexia, Monaco explored the connection of the KIAA0319 gene to the disorder. He explained the influence on the variations at the KIAA0319 locus on development in the cerebral cortex and cerebellum.

Neurons within malfunctioning KIAA0319 are unable to migrate properly. However, like every other neurodevelopmental disorder, dyslexia is not caused solely by the KIAA0319. Monaco stressed the importance of this concept in his closing statements.

"Genes are not prescriptive of behavior," he said. "They don't go straight from DNA to behavior, there are a lot of steps in between."