New Autism-Causing Genetic Variant Identified
Release Date: March 25, 2015
Using a novel approach that homes in on rare families severely affected by autism, a Johns Hopkins-led team of researchers has identified a new genetic cause of the disease. The rare genetic variant offers important insights into the root causes of autism, the researchers say. And, they suggest, their unconventional method can be used to identify other genetic causes of autism and other complex genetic conditions.
A report on the study appears in the April 2 issue of the journal Nature .
In recent years, falling costs for genetic testing, together with powerful new means of storing and analyzing massive amounts of data, have ushered in the era of the genomewide association and sequencing studies. These studies typically compare genetic sequencing data from thousands of people with and without a given disease to map the locations of genetic variants that contribute to the disease. While genomewide association studies have linked many genes to particular diseases, their results have so far failed to lead to predictive genetic tests for common conditions, such as Alzheimers, autism or schizophrenia.
In genetics, we all believe that you have to sequence endlessly before you can find anything, says Aravinda Chakravarti, Ph.D. , a professor in the Johns Hopkins University School of Medicines McKusick-Nathans Institute of Genetic Medicine. I think whom you sequence is as important if not more so than how many people are sequenced.
With that idea, Chakravarti and his collaborators identified families in which more than one female has autism spectrum disorder, a condition first described at Johns Hopkins in 1943. For reasons that are not understood, girls are far less likely than boys to have autism, but when girls do have the condition, their symptoms tend to be severe. Chakravarti reasoned that females with autism, particularly those with a close female relative who is also affected, must carry very potent genetic variants for the disease, and he wanted to find out what those were.
The research team compared the gene sequences of autistic members of 13 such families to the gene sequences of people from a public database. They found four potential culprit genes and focused on one, CTNND2, because it fell in a region of the genome known to be associated with another intellectual disability. When they studied the genes effects in zebrafish, mice and cadaveric human brains, the research group found that the protein it makes affects how many other genes are regulated. The CTNND2 protein was found at far higher levels in fetal brains than in adult brains or other tissues, Chakravarti says, so it likely plays a key role in brain development.
While autism-causing variants in CTNND2 are very rare, Chakravarti says, the finding provides a window into the general biology of autism. To devise new therapies, we need to have a good understanding of how the disease comes about in the first place, he says. Genetics is a crucial way of doing that.
Chakravartis research group is now working to find the functions of the other three genes identified as possibly associated with autism. They plan to use the same principle to look for disease genes in future studies of 100 similar autism-affected families, as well as other illnesses. Weve shown that even for genetically complicated diseases, families that have an extreme presentation are very informative in identifying culprit genes and their functions or, as geneticists are taught, treasure your exceptions. Chakravarti says.
This work was funded by grants from the Simons Foundation, the National Institute of Mental Healthand an Autism Speaks Dennis Weatherstone Predoctoral Fellowship.
See original article for other authors on the paper :
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First, I would like to brag a bit. My daughter was an intern in this lab and worked on this project
Second, this might explain the mystery of autism. My nephew has aspergers, and it showed even when he was a toddler. To find out that the changes are part of the brain's development is utero, is an important finding.
Great article Jerry.
And it does seem epidemic or has it always been this way only undiagnosed as autism? Seems there are so many more children with autism. Could it be something the parent was subjected to like in the 60's and 70's? I certainly don't know, but to find a cure or prevention for Autism, Alzheimer's, Schizophrenia and other similar disease would be wonderful. Great article Jerry.
In some families some grow older without any indication of any of these disease while a sister or brother are burdened by one of them. Strange, my grandfather on my daddy's side lived for 95 years and his mind was sharp as a knife. He had three sisters. One died at about 90 from a heart attack. One was just like him and lived into her 90's. The other one developed Alzheimer's in her early 80's and recently passed away.
I have a nephew that is autistic, he is now an adult and is doing fine. He was a wonderful, fascinating, brilliant child as he grew up. Everybody in the family loves Matt.
I was first introduced to autism when I was selling real estate back in the 70's. I met to author Barry Neil Kaufman through a fellow Real Estate agent. Barry had written a best selling book called Son-Rise about his 5 year old autistic son, Raun, and was looking for a suitable site to build a learning center for autistic children. I couldn't find a listing in our market area that met the particular requirements he was looking for, so I referred him to an agent in Massachusetts who found him the site that is now the location of the Autism Treatment Center of America . Today Raun Kaufman is the Director of Global Education for the Autism Treatment Center of America.
Barry kaufman has since written a sequel " Son-Rise; The Miracle Continues ". The link will take you to the forward written by Raun, and allows free access to the entire text of the book.
Wow! You ought to be proud, Johns Hopkins is veryprestigious medical center to be associated with.
That your daughter was an intern on this particular project is amazing.
The anti-vaccine crowd are shallow thinking, paranoid nit-wits and a virtual amenaceto society.
As kid I went to bed every night wondering if I was going to wake up paralyzed with Polio.
I will never forget my lifetime hero, Dr. Jonas Salk, of all the vaccinations I've had in my life, that one was special.
I think autism has always been at bout the same level, but, as you indicate Six, doctors have only more recently been able to identify that these children do not simply have "retarded" development as previously thought.
Great article Jerry! Perrie, I'm sure you are extremely proud of our daughter, and have every right to be!!
Thanks Nona. The release of this report by Johns Hopkins is very timely, as April is World Autism Awareness Month.
I agree. I think the increase in Autism is really a deeper understanding of it and that more and more children and adults who were once considered to be"retarded" are now being more correctly diagnosed as having a form of Autism.This proper diagnoses means better treatment for them.
correction...."your daughter"
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