Two top autism genes may have a mechanism in common
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ASPartOfMe
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Joined: 25 Aug 2013
Age: 66
Gender: Male
Posts: 34,465
Location: Long Island, New York
Quote:
Mutations in two genes linked to autism and intellectual disability may boost the immune response and cause synapse dysfunction, according to unpublished research.
Researchers presented the findings virtually yesterday at the 2021 Society for Neuroscience Global Connectome.
People with a mutation in the gene ADNP or POGZ often have autism and intellectual disability. Previous research has shown that a mutation in either gene increases the expression of other genes, but it was unclear how such changes lead to an individual’s traits.
To study the effects of ADNP and POGZ mutations, Conrow-Graham and her colleagues developed short pieces of RNA that silence either of the two genes. They engineered a virus to carry these pieces of RNA into cells, injected the modified virus into the medial prefrontal cortex of 4-week-old mice and then evaluated the animals’ behavior and synaptic function.
The medial prefrontal cortex is thought to be involved in social behavior and cognition. Mice with silenced ADNP or POGZ genes performed worse than controls on tests of spatial reasoning and memory, but not on tasks of general motor function, suggesting that the loss of the genes resulted in cognitive impairments.
The team also used RNA sequencing to examine how the loss of ADNP or POGZ affects gene expression. As expected, they found that mice with a silenced gene had higher expression levels of other genes throughout the brain than controls did.
And when the team assessed the differentially expressed genes according to their function, they found that the largest differences occurred for genes related to immune response and inflammation. Previous research has shown that people with neurodevelopmental disorders also tend to have increased expression of genes that fall into this category.
Researchers presented the findings virtually yesterday at the 2021 Society for Neuroscience Global Connectome.
People with a mutation in the gene ADNP or POGZ often have autism and intellectual disability. Previous research has shown that a mutation in either gene increases the expression of other genes, but it was unclear how such changes lead to an individual’s traits.
To study the effects of ADNP and POGZ mutations, Conrow-Graham and her colleagues developed short pieces of RNA that silence either of the two genes. They engineered a virus to carry these pieces of RNA into cells, injected the modified virus into the medial prefrontal cortex of 4-week-old mice and then evaluated the animals’ behavior and synaptic function.
The medial prefrontal cortex is thought to be involved in social behavior and cognition. Mice with silenced ADNP or POGZ genes performed worse than controls on tests of spatial reasoning and memory, but not on tasks of general motor function, suggesting that the loss of the genes resulted in cognitive impairments.
The team also used RNA sequencing to examine how the loss of ADNP or POGZ affects gene expression. As expected, they found that mice with a silenced gene had higher expression levels of other genes throughout the brain than controls did.
And when the team assessed the differentially expressed genes according to their function, they found that the largest differences occurred for genes related to immune response and inflammation. Previous research has shown that people with neurodevelopmental disorders also tend to have increased expression of genes that fall into this category.
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Professionally Identified and joined WP August 26, 2013
DSM 5: Autism Spectrum Disorder, DSM IV: Aspergers Moderate Severity
It is Autism Acceptance Month
“My autism is not a superpower. It also isn’t some kind of god-forsaken, endless fountain of suffering inflicted on my family. It’s just part of who I am as a person”. - Sara Luterman
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