Most of these 102 genes were expressed in the brain, and affect synapses or regulate other genes. This means they have important roles in switching other genes on and off.
Furthermore, 49 of these genes are also linked to other developmental disorders, underlining the fact that the neurobiology of many such conditions are likely to overlap.
A mammoth study
The research published on Thursday in Cell, a scientific journal, revealed the discovery, which represents a significant leap forward in understanding the neurobiology of autism. It represents a 57% increase in the number of genes known to be associated with ASD since 2015. It was centred at the Mount Sinai School of Medicine in New York, but required a massive international collaboration, taking in scientists from over 50 locations worldwide.
This study used large-scale exome sequencing. In this technique, instead of gathering all of a person’s DNA sequences, only the relatively small portion that codes for RNA and proteins is analysed. In this way, resources can be used more efficiently, and all of the most important DNA regions of tens of thousands of participants can be compared and contrasted.
Over 35,500 people had their entire exome sequences, including almost 12,000 people with ASD. The Autism Sequencing Consortium was behind the collection of this largest-ever database of the DNA of people with ASD.
When a large proportion of the 12,000 people with ASD in the database share a mutation at a specific location, and most of the healthy people lack it, it is flagged by the computer system. In this way, over 100 genes were implicated in ASD.
Picking apart the mystery
This study threw up some other novel discoveries. The authors used an improved computer system to allow them to discriminate between mutations inherited from a parent, and new or de novo mutations arising when eggs or sperm are created. It also allowed them to dissociate some of the genes linked to autism risk from those linked to other developmental and intellectual disabilities. This will help shed light on the core deficits of ASD.
Dr Joseph D. Buxbaum, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai, said: “With these identified genes, we can begin to understand what brain changes underlie ASD and begin to consider novel treatment approaches”. Those treatments could target the disease pathway of a particular gene or genes, for example by delivering essential proteins to the brains of autistic people who lack them.
With the advent of Crispr-Cas9 gene editing technology, however, there may soon come a time when the genes themselves can be altered in the living brain of affected children. It may be some way off yet, but the nature of gene editing means that when it does reach the clinic, it will form the basis of some truly remarkable therapies. “New drugs will be developed based on our newfound understanding of the molecular bases of autism” said Dr Buxbaum.
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Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
Summary
We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less.
Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences.
Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
Graphical Abstract
Carol graduated from Riverside White Cross School of Nursing in Columbus, Ohio and received her diploma as a registered nurse. She attended Bowling Green State University where she received a Bachelor of Arts Degree in History and Literature. She attended the University of Toledo, College of Nursing, and received a Master’s of Nursing Science Degree as an Educator.
She has traveled extensively, is a photographer, and writes on medical issues. Carol has three children RJ, Katherine, and Stephen – one daughter-in-law; Katie – two granddaughters; Isabella Marianna and Zoe Olivia – and one grandson, Alexander Paul. She also shares her life with her husband Gordon Duff, many cats, and two rescues.
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Looks like Carol has caught Gordon’s disease. That’s a notifiable condition.
Regarding Gordon Duff’s note:
One one hand “…found the filthy hand of the Deep State behind the AntiVaxx movement at every turn…”;
On the other hand “…have always suspected vaccines, often cheaply made, expired, fake…”.
Are not both hands connected to the same head, with the first used to discredit the legitimate arguments of the critics of the second?
But the result of trying to discuss the subject of vaccines is to run into firm believers of each camp who will accuse the rational person of speaking in code for one side or the other, the only response to (since pistols at dawn is not legal, no do we have the libel laws of Victorian Great Britain) is “You called me a liar, GFY).
But that seems true of most online discussions where keyboard warriors have no trouble flinging crap that would earn them an ambulance ride in the real world.
Im sitting on the fence on this but like a commentator said is it possible that vaccines trigger the genes that are responsible for ASD in some children who have genes that are more susceptible to the vaccines chemicals? Seems like its a possibility considering that people are susceptible to heart problems if there is a family history of it, or certain cancers, or mentle ailments. One shouldn’t throw out the baby with the bath water on this one yet.
The Russians propagated SV40 associated with the Polio vaccine well after it was established as a carcinogen. And used it on millions.
..Maybe it is a fair statement to say that we, the non-autistic, don’t really know what goes on in the minds of the autistic. As, for the most part, the autistic are not able to articulate what their perception of reality is. But we have seen that a portion of the autistic people are able to access parts of their brains that give them mental abilities that we consider to be genius. What I am about to conjecture was not read out of a book or article, but straight from my imagination. Geniuses are autistic. They are the autistic that are able to function in his mess we call society while still being able to tap into that portion of their brain that separates them from quote unquote normal people. I am just saying that in my imagination you can’t have one without the other. No autism, no genius. Where does that leave us?……
It is so funny that VT involves it self in things they do not understand.
If a disease is expression of some genes it does not mean that the cause is only genes. There are trigger factors which facilitate that some people get the disease but not others.
To make a judgement so joyfully because of one study, shows the luck of scientific understanding. If people know how studies are done. There are many studies on the same subject with opposite results.
So we have to wait and not jump on a final conclusion in a infantile manner.
Cyruss, We are fully aware that environmental factors can also come into play for autism. Autism is also very genetically based and that has been proven long before this article. Like Alzheimer’s disease, autism has become epidemic and all focus should be on how to avoid/change whatever is causing these diseases.
What they are not making clear, is that certain genes are more prone to autism, but that it is environmental factors which then cause it. It is like how some of us put on weight easily, but will still need to eat the high carb foods and sugars to get fat, just like the people with autism genes have to have the vaccines, antibiotics, glphosphate, junk food etc to become autistic.
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