Home > Science > New CNVs on Chromosome X

New CNVs on Chromosome X

Guest blog by Dr. John Vincent, who is a Scientist and Head of the Molecular Neuropsychiatry and Development Laboratory of the Psychiatric Neurogenetics Section in the Neuroscience Research Department and an Associate Scientist of The Centre for Applied Genomics at The Hospital for Sick Children, Toronto.

The group here in the Molecular Neuropsychiatry & Development Lab at CAMH, along with our collaborative partners at Sick Kids and elsewhere report the identification of PTCHD1 as a gene for autism spectrum disorder, as well as intellectual disability, on the X-chromosome. The finding stems from attempts to find differences in specific strands of DNA, called copy number variants (CNVs) in the DNA of autistic individuals that might be linked to the condition. If the human genome can be thought of as a book containing the DNA code written out in words and sentences, we each of us have our own unique book, with many words spelled differently from each other, but mostly without changing the overall meaning of the words and sentences. Traditional genetic studies would try to identify spelling mistakes that compromise the meaning of a sentence, and thus lead to an incorrect message, i.e. resulting in a clinical condition. In our current study we have been looking instead for whole sentences, paragraphs or pages that are either deleted or duplicated (i.e. CNVs), thus altering the meaning of the message, and leading in this case to autism.

We were particularly interested, in our study, to look at CNVs on one of the 2 sex chromosomes, the X, as it might explain some of the bias towards boys having autism over girls. In our initial screen of over 400 autism patients, we identified a large deletion disrupting the PTCHD1 gene. In an analysis of CNVs in genomes from over 1000 more autism individuals, deletions just next to this gene were the most significant finding. These deletions are likely to disrupt DNA sequences that may regulate how the PTCHD1 gene is expressed. In addition, we identified many single letter changes in the PTCHD1 gene that may affect the “meaning”. These changes were not found in the DNA of many control individuals.

The PTCHD1 gene makes a protein with as yet unknown function, however it shows similarities to several known proteins that function as cell-surface receptors for an inter-cellular signaling pathway known as Hedgehog, crucial in determining how brain cells develop and mature. The preliminary data we present in the paper shows that PTCHD1 appears to have similar properties to the two Hedgehog receptors already known, leading us to speculate on a role for Hedgehog-related processes in autism.
These findings give us another important gene that we can screen for in at risk children, and will allow earlier therapeutic interventions, thus increasing the likelihood of success.

For more information, please see the press release.

Categories: Science Tags: , , ,
  1. Loramath
    September 17, 2010 at 4:02 am

    Thanks for your hard work.

  2. Marleen
    September 17, 2010 at 8:24 am

    This is a fantastic begining to hopefully finding a cure. If not, certainly screening for the gene. My son was different from birth; with severe food allergies. Thankfully, he is doing well – he is high function, and quite an outgoing individual.

  3. September 17, 2010 at 8:59 am

    I am happy to see this study released almost at the same time that the MMR vaccine was proven not linked to autism. It is important for us to focus on facts that can help us reach a solution, or as the article suggests, leading the way for an earlier diagnose and treatment.

  4. Noreen
    September 17, 2010 at 9:07 am

    Why are we seeing so MANY more deletions in this generation. So many children spinning in circles, instead of learning like a typical kid? Why has the rates skyrocketed and what is causing problems with proteins and how this generation can’t breakdown things? So many questions on what is altering our DNA so much and so radically. 1 in 60 here in NJ if your a boy. We better get some answers and quick.

  5. Sally D.
    September 17, 2010 at 9:43 am

    I’m so happy that we’re getting closer to possible causes for ASD. It sounds like genes play an important part is autism. I’ve blamed myself for years for my daughter’s autism. I was prescribed an SSRI antidepressent during my 2nd and 3rd trimester of my pregnancy. Could moter’s taking antidepressants during pregnancy cause autism?

  6. Katie Wright
    September 17, 2010 at 11:01 am

    The MMR was not proven to be unlinked to autism. A small percentage of children, like mine, had horrific reactions. And early diagnosis and treatment did not make an impact on my son.

    Valeska, everyone’s child is different. We need autism research that reflects the whole spectrum of experiences. Autism has not risen 1,000% in the past decade because of spontaneous changes to our genes. That is the symptom, not the cause. We need to find the cause, which must be largely environmental because genes alone cannot account for these skyrocketing numbers.

    We need to study the effects of environmental insults on testosterone. Testosterone, ironically, is much more delicate than estrogen. Estrogen serves a protective purpose, while testosterone quickly binds with toxic substances like heavy metals, making boys more vulnerable to environmental insults- especially boys with a family history of autoimmune disorders.

    • Cheri
      September 17, 2010 at 3:07 pm

      Well said thank you for a description most of us can relate with.
      Everyone is different I rule out nothing based on my personal experience.

  7. drew
    September 17, 2010 at 11:34 am

    Do tests exist yet to identify if these CNVs exist for families with children of autism so that they might test younger children yet to be diagnosed?

    Also, outstanding findings and congrats to the teams involved.

  8. Jennifer
    September 17, 2010 at 11:38 am

    IS it any wonder that our DNA is changing or manipulating or even failing us. We were never meant to live the way we do here in the West. We breath in and ingest all kinds of chemicals and preservatives. Let’s take pesticides for example; Eating one apple a day with pesticide residue on it may not be a big deal, your body can flush out the toxins but when almost everything we consume has some sort of toxin in it that our bodies need to flush out, it is bound to build up and overflow. Not to mention what flushing out all those toxins do to an unborn child who’s liver and kidneys are not yet developed. They do no testing on children, babies, or fetuses with these chemicals. Not to mention our food and water are not the only contaminates in this variable. Our air is not as clean as it once was and we are constantly exposed to wireless waves in our phones, microwaves, computers, and all of our other technologies that make our lives easier.
    I have a friend that calls what has happened; “The Perfect Storm”. So many outward variables have contributed to the change in our DNA. More and more people are being diagnosed with food allergies, environmental allergies, digestive problems, and auto immune problems, then ever before. I don’t remember as a child one person allergic to peanuts or dairy, not to mention wheat or glutton.
    Now with all this being said, I am not a Doctor or have any medical degrees, I am just a Mom of a Son with Autism. I have have spend many nights lying awake thinking about this disorder that has griped our family. I am sure most of you reading this are in the same boat.

    September 17, 2010 at 12:57 pm

    My child has a specific genetic deletion (SHANK 3). The disorder is known as 22Q13 Phelan McDermid Syndrome (www.22q13.org).
    This deletion is one (and one of the only) scientifically proven cause for autism (http://www.autismspeaks.org/science/science_news/shank3_mutations.php).

    I belong to a foundation (www.22q13.org) which is currently sponsoring some exciting research in this area (including an open source bio repository and registry) which is one of the first of its kind specific to this condition. The research is already leading to treatments (http://www.sciencedaily.com/releases/2010/05/100520131547.htm)

    Looking at the genome is currently the MOST PROMISING, scientifically backed road to finding answers and eventual treatments.

    If you are interested in forwarding the research or helping in the effort to discover treatments, please become informed and involved…Research is both time consuming and extremely expensive, funding from the NIH is being cut every day and most of us involved have severely special needs children at home requiring our constant attention…any and all help (even if just to inform the community) is greatly appreciated.

  10. Michelle Roberts
    September 17, 2010 at 1:51 pm

    This is a GREAT start. My fabulous and adorable 6 year old nephew was diagnosed with Autism at the age of 3 and to see all the obsticals he has conquered along the way floods my heart with great joy. I am on websites almost every day learning as much as I can. I thank ALL OF YOU out there that are researching and trying to find as many answers as you can to a lot of unanswered questions that many may have.

  11. Pauline
    September 17, 2010 at 2:31 pm

    Thank you all so much for your exceptional expertise. I wish I could give you 2 million dollars. 1 million towards your research and 1 million to include my son, Quinn, who is now in a care home. Best choice? Maybe as he’s high-risk danger to himself and refuses to remain contained i.e. hopping 6′ fences like you or I can step over a crack on a sidewalk. Has tried to set himself on fire. Has broken a few windows. Back to best choice? Logically yes. As his mommy? I feel terrible and even with all of the above, I so miss him dearly. God Bless all of you. I pray that in our life time my husband, myself, and our #1, Quinn will be able to experience his coming home one day. How many stars are up in the sky? That’s how many times I thank you. With my utmost respect and sincerity, – Pauline – To the mommy that has experienced gripe? I’m with you, but please count your blessings. My creepy family? Dropped us as soon as our son was diagnosed. Why? Their kids are perfect. May they not rest in Hell.

  12. sheena greiner
    September 22, 2010 at 1:23 pm

    I am excited to see all the new research available on autism.. I have great concerns about exactly what will be done with this information. Genetic screening like we see for down’s syndrome in the future???? When was the last time you saw a young child with down’s syndrome? Trisomy 21 has not been cured….just eliminated. Do we really want this for our children with autism??

  13. Prafulla Sharma
    September 26, 2010 at 7:05 am

    I have a daughter aged 13 years and a son aged 6 years. My daughter was mildly autistic but has managed to go to a regular school and is doing o.k. in studies. But she still has communication problems and cannot form sentences correctly while speaking. The same problem is with my mother who is 64 and has had trouble in communicating properly throughout her life.

    My brother and sister are normal (just like me) and have excellent communication skills. My sister in fact is a very good orator. Both of them have kids who have no problem. But my 6 year old son is severely autistic. He can speak only a few words and is very hyperactive. My wife is very short tempered and must have been hyperactive as a child (she still is to a great extent). But her sister’s son is normal.

    I think that it must have been due to our genes. Are we both carriers (just like Thallesemia carriers do not show any symptons but their children have full blown symptoms)

  14. autismspeaksfan
    October 23, 2010 at 3:17 am

    Go to you tube: type in “Behaviorally Fragile Autistics” on you tube. This is a most interesting caes of autism, self injurious behavior and seizures. Very complex, but not without hope. There are some very important points seen in videos that would help professionals and anyone working with this unique population. This case has had numerous MRIs. cat scans, genetic work ups, cbcs, etc..all to no avai. According to mom, and evidence she presents in some videos, the child has had extensive medical and behavioral work ups, yet continues to stump the “experts.” It’s seems a case like this truly stumps us, because the fact is this type of autism requires round the clock care, analysis and daily acute and PRN medications to mitigate the self abuse that has plagued this autistic child for severeal years. A most interesting case.

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