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New Genetic Clues to Autism


There is a long, controversial life to autism. Autism comes from the greek autos, meaning self. The term describes conditions which a person is removed from interaction — hence, an isolated self.

It was first described by a guy named Eugen Bleuler, a swiss psychologist who noticed the symptoms in a schizophrenic patient. Technically Autism is a particular diagnosis in the Autistic Spectrum which includes things like Asperger syndrome, there is even something called savant syndrome in which children display amazing abilities in a particular field [typically math or music] with no real training.

There was also a claim that there is an explosion in the autistic spectrum cases, with no clear cause. The truth is that between better techniques in diagnosis combined with the change in definition to include more people, there probably has been very little change in the prevalence of the disorders.

The cause of autism has always been in question leading to different amounts of hysteria regarding the disorder [like the BS link to vaccination which, despite being shown as false still scares people]. Thankfully just recently science has discovered a genetic link to the disorder.

Now thanks to an amazing feat of science [and probably a lot of late nights in front of tons of data] there have been three different gene networks linked to autism. These networks may offer attractive targets for developing new autism drugs or even repurposing existing drugs that act on components of the networks.

Interestingly enough, one of the autism-related gene pathways also affects some patients with attention-deficit hyperactivity disorder (ADHD) and schizophrenia—raising the possibility that a class of drugs may treat particular subsets of all three neurological disorders.

“Neurodevelopmental disorders are extremely heterogeneous, both clinically and genetically,” said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia (CHOP). “However, the common biological patterns we are finding across disease categories strongly imply that focusing on underlying molecular defects may bring us closer to devising therapies.”

The current research they are doing is a genome-wide association study comparing more than 6,700 patients with autistic spectrum disorder to over 12,500 control subjects. This was one of the largest-ever studies of copy number variations [CNVs] in autism.

[Loony Hint: CNVs are deletions or duplications of DNA sequences. Which is different from single-base changes in DNA, in that there is more than one base pair being changed or deleted.]

The study team focused on CNVs within defective gene family interaction networks [ or GFINs for short]—groups of disrupted genes acting on biological pathways.

In patients with autism, the team found three particular GFINs in which gene variants actually changed how genes interact with proteins. Of special interest to the study group was the metabotropic glutamate receptor [mGluR] signaling pathway, defined by a particular set of genes [already known by science] that affects the neurotransmitter glutamate, a major chemical messenger in the brain regulating functions such as memory, learning, cognition, attention and behavior.

The team of researchers involved in this study and other investigators previously reported that 10 percent or more of ADHD patients have CNVs in genes along the glutamate receptor metabotropic [GRM] pathway, while still other teams have implicated GRM gene defects in schizophrenia.

Based on these findings, Hakonarson is planning a clinical trial in selected ADHD patients of a drug that activates the GRM pathway.

“If drugs affecting this pathway prove successful in this subset of patients with ADHD, we may then test these drugs in autism patients with similar gene variants,” he said.

In ASDs and other complex neurodevelopmental disorders, common gene variants often have very small individual effects, while very rare gene variants exert stronger effects. Many of these genes with very rare defects belong to gene families that may offer possible drug treatment avenues.

For those interested, the three gene families found in the current study have notable functional roles. [Warning, sort of hardcore science ahead] The MXD-MYC-MAX gene network is involved in cancer development, and may be the cause of links reported between autism and specific types of cancer. The CALM1 network includes the calmodulin family of proteins, which regulate cell signaling and neurotransmitter function. Finally, members of the GRM gene family affect nerve transmission, neuron formation, and interconnections in the brain—processes highly relevant to ASDs.

The functional activities identified in the current study are consistent with a recent multicenter study in which Hakonarson participated, published May 1 in the American Journal of Human Genetics.

That study, led by scientists from Paris and Toronto, and using Autism Genome Project data, found hundreds of rare ASD-related gene variants converging on gene networks involved in neuronal signaling, synapse function and chromatin regulation [if you read the other autism post you know, but chromatin regulation is a biological process affecting gene expression].

Another interesting thing to note, many of the genes in these networks have been implicated in other developmental disorders besides autism.

“Even though our own study was large, it captures only about 20 percent of genes causing ASDs,” said Hakonarson, who added that still larger studies are needed to further unravel the genetic landscape of autism. “However, strong animal data support an important role for the glutamate receptor pathway in socially impaired behaviors modeling ASDs. Because the GRM pathway seems to be a major driver in three diseases– autism, ADHD and schizophrenia–there is a compelling rationale for investigating treatment strategies focused on this pathway.”

HUGE thank you to the amazing work done by Autism Speaks, without their help and commitment to the project, this work would have never been done.

And once more [because I can], this is exactly why we don’t accept correlation as cause. If we did, we would be back in the stone ages not vaccinating our children and wondering why there are still autistic children being born. Just because it’s an easy thing to grasp and demonize does not make it so. With that said, vaccinate your children please, for their health.

Suck it anti-vaccination people.

All that hard core science not hard core enough? You probably want the full study –here!

Hakon Hakonarson (2014). The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism, Nature : http://doi.org/10.1038/ncomms5074

One response

  1. Pingback: Finally! A Definite Cause of Autism: Hint it isn’t Vaccines | Loony Labs

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