Home > Science > Autism and Chromosome 15

Autism and Chromosome 15

About one in every 10,000 babies is born with two few or too many genes on chromosome 15.  The likelihood that these babies will be on the autism spectrum is as high as 80%, making these rare genetic events a target for autism research.

Gene targets.  Of the estimated 30,000 genes that make up the human genome, between 700-900 genes lie on chromosome 15.  Specific segments of this chromosome are associated with autism, narrowing the number of genes of interest to fewer than 30.  These genes are located on the long arm of chromosome 15, called q.  The most studied region so far is known as 15q11-13, where 11-13 describes an exact physical location on the chromosome (the region in red in the picture).   Sometimes babies will have extra copies within this area, beyond the normal two parental 15q11-13 regions, resulting in 3, 4, 5, or even 6 extra copies of all the genes in the duplicated region.  In other cases, portions of this region are deleted, leaving no copies of these genes.

How do chromosome copy variations occur?   Autism Speaks interviewed a key researcher, Dr. Carolyn Schanen, in an article ‘Understanding the Role of Chromosome 15 in Autism’, that explains these events in detail (link to e-Speaks).   The basic concept is that, during cell division, the DNA sequences of our chromosomes literally break apart and recombine; during this process, sometimes there is an aberrant duplication of genetic material.  Some forms of 15q11-13 duplications are inherited and some occur in the child and are not found in the parents.  Sorting out all of the possibilities is one of the goals of the research of 15q duplication and deletions.

Overlapping syndromes in 15q11-13. Deletions of genes in the 15q11-13 region are associated with Angelman’s Syndrome or Prader-Willi Syndrome, whereas duplication of such genes results in a different syndrome (15q11-13 Duplication Syndrome).  A syndrome is named when common physical features or behaviors are observed.  Prader-Willi occurs in about 1 in every 10,000 births and is characterized by hypotonia, hyperphagia (obsessive eating = characteristic weight gain) and diagnosis of an Autism Spectrum Disorder (ASD) in 25-45% of individuals.  The occurrence of Angleman Syndrome is about 1/12,000 and is characterized by sleep disturbance, ataxia (unstable walking), frequent laughter, excitable personality and hand flapping movements.  ASD is also linked with this syndrome.

Babies with 15q11-13 duplications typically have hypotonia (low muscle tone), minor facial differences (nose, eyes, ears), intellectual disability and are diagnosed with autism spectrum disorder.  Seizures can be present in the newborn or develop later resulting in epilepsy that is hard to control, and sometimes lethal.

What are these genes doing? A gene’s job is to be a faithful blueprint of information, such as the code for the production of a protein.  The level of production of any particular protein is carefully regulated by the cell and irregularities in the levels of proteins can impair cell function, or even lead to cell death.

For example, the product of gene UBE3A in the 15q11-13 region is involved in targeting proteins to be broken down (degraded) within cells and deficits are linked to brain pathology in both Angelman’s Syndrome and autism.  Another gene in the region, called ABPA2, makes a protein crucial in getting neurotransmitters out of neurons.  And the CHRNA7 gene is an acetylcholine receptor that mediates fast signal transmission at synapses.  The general idea is that too little of these gene products would be linked to low muscle tone and ataxia.  A new report from an international group shows that deletion of genes at 15q13.3 is linked to epilepsy.  Three genes in the 15q11-13 region make protein subunits that need to aggregate with other subunits to form the receptor for the brain’s main inhibitory neurotransmitter, GABA.  The extra copies are thought to create an unstable receptor and the lack on inhibition leads to excessive cell firing (seizures).  Researchers are just beginning to measure gene products in brain cells of those with 15q duplications.

Changes in the brain. A special project evolved to thoroughly examine postmortem brain tissue of young adults and children with 15q duplications.  In 2006, sudden deaths in otherwise healthy individuals with 15q duplications created a concern about mortality risk in these families (Isodicentric 15q Exchange Advocacy and Support–  IDEAS) posted a Physician Advisory on their site at to provide information to concerned parents.  The group also encouraged families to request an autopsy in the event of death as well as brain donation to the Autism Speaks’ Autism Tissue Program (ATP).   Since then there have been 10 brain donations and in collaboration with the New York Institute for Basic Research, this tissue has been made available for research.  The preliminary results show a disorganization of cell production and placement.  The arrow in this picture of a brain section of a preadolescent boy shows a whole extra row of cells that are not typically seen in a region of the hippocampus termed the dentate gyrus, an area of the brain associated with memory and attention functions.  Disturbances of brain architecture like this are linked to alterations in brain cognitive function, and often to seizure activity.

Many more changes have been observed that will be described as the research continues.  The goal is to link anatomical changes to specific types of gene copy variations and behavioral characteristics linked to autism that include social deficits, communication deficits, ritualistic behaviors, mental retardation, aggression, anxiety, epilepsy, sensory abnormalities, sleep disorder as well as unique abilities.  These behaviors are generated by the brain and it will take time, effort and funds to keep up with the discovery of syndromes identified by chromosome copy variations (an abnormal number of chromosomes is called aneuploidy) and the particular characteristics of those with the disorders and the patterns of brain changes seen by researchers.

This understanding of how genes contribute to physical features and behavioral characteristics requires ongoing support by dedicated families who are partnering with scientists to help better understand their child’s disorder.  With increased understanding of the underlying biological processes, we may someday be able to develop treatments that can significantly reduce the impairments associated with these conditions.   Contribution of biomaterial resources like DNA and brain donation is vital to this effort.

Additional reading.   An excellent open access article by another of the science advisors, Agatino Battaglia, is  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613132.  Brain research papers by investigators focused on autism and related disorders are posted on www.atpportal.org.

Autism Speaks’ Autism Tissue Program supports specialized neuropathology  research by providing approved scientists access to the most rare and necessary of resources, post mortem human brain tissue. We wish to recognize the commitment and generosity by our ATP donor families. More information can be found at www.autismtissueprogram.org or call 877-333-0999 for information or to initiate a brain donation.

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  1. Mary
    August 16, 2010 at 1:47 pm

    Where can this test be administered?

  2. Katie wright
    August 16, 2010 at 5:12 pm

    There is nothing unusual about the genes of 90 percent of people w asd. We have been investing so heavily in this gene route forever and not making progress. This work is interesting but ultimately useful to so few.

    Study what happened to our kids after they were born. My child developed autism he was not born with autism.

  3. Katie Wright
    August 16, 2010 at 8:52 pm

    Re-reading this and found “ways of linking anatomical changes to chromosomal abnormalities.” This is borderline offensive.

    There is nothing wrong w/ the chromosomes or anatomical features of our kids. Prader Will and Angelman are not autism- not even close. They are rare genetic disorders that are not rising. This bizarre obsession to desire to force autism into an ill fitting genetic pigeon hole is unhelpful and greatly frustrating. Do these scientists actually spend time w/ a wide variety of ASD kids? Have they talked to Moms of singletons, sick kids, kids who developed normally? Have they spent any time watching before and home movies? Have the asked the parents of kids under 10 what they think triggered their child’s autism? Have they studied the medical records of chronically ill ASD kids?

    We all have genes that can be turned on or turned off. The problem is understanding what environmental triggers are suddenly turning certain genes on- genes that have been dormat for generations. Why are mito disorders suddenly exploding amongst kids developing regressive autism? Why are all these parents reporting that their children were fine until the febrile seizures, multi day long fevers following a multiple vaccination? Why then do the latent mito disorder develop? Could it be because the immune system had been overtaxed by too many viruses- often live and preserved at once? Why do so many children like Hannah Polings have autoimmune diseases in their family history? What is turing on these genes and making a previously healthy child chronically ill?

    We can do nothing- nothing about our genes. What we can do and what we need to do is understand that autoimmune diseases are clearly a huge biomarker risk factor for serious adverse vaccine reactions and hence, regressive autism. Moreover we need to study the immune challenges posed by such a huge combination of live, preserved and multi dose viruses in conjunction w/ 25 unresearched toxic adjuvants.

    I would absolutely donate tissue, brains any bodily parts that could be of use to this program. But please stop framing autism as a heritable genetic disorder of the brain. That was autism in 1990 maybe- that isn’t autism today. Autism Tissue Program personnel should join thousands of families at the NAA family and medical research research conference this fall. Come and learn about how other neurologists, geneticists and other researchers are studying these issues.

  4. Bart
    August 17, 2010 at 11:56 am

    You do not believe, Katie, that some people are born on the Autism Spectrum?
    Whether or not your child was vaccine injured does not make it so for everyone on the spectrum.

    I do want to know how people believe this research is beneficial to society right now, however. I also would like to know why IAN is hailed? IAN as far as I know is an online discussion forum where people talk about research or tell about their Autism experience for purposes of research. I am also creeped out by this tissue program. Asking for people’s tissue so we can concoct a “prevention” screening to detect if someone may dare to be born different?

  5. Katie Wright
    August 17, 2010 at 12:17 pm

    Good point, I should have said I am looking for research investment parity in vaccine injured kids.

    I have no idea about IAN or tissue prevention- useful questions

  6. August 18, 2010 at 11:54 pm

    I believe autism is genetic in nature. Looking back at my 30 month old son, it is apparent that right from about 3-4 months, he was a “little different”, and we realized how different when he was officially diagnozed with ASD at about 20 months.

    Our child was always hypotonic (still is), always had poor eye contact etc., among others, and fails most “Autism criteria tests” (meaningfully definitely autistic)

    I am cautiously optimistic this research will yield results – hopefully in next 5 years or less. In the meantime, back to ABA and therapies, as well as floortime.

    BTW, I do not believe vaccines cause autism , neither do milk products impact autism severity (at least in majority of autism cases). We have been led down the wrong path for too long, and it is time we started listening to the research.

  7. Piper Lyon
    August 20, 2010 at 11:09 am

    I, myself, find this all very interesting. My son was diagnosed with Autism at around 2 years, and it was when he was 14 years old that we were informed of his 22q13 Deletion Syndrom. This too, has Autistic characteristics and severe mental retardation. So, my feeling is that Autism could very well be genetic and we all need to be open minded. I was just thankful I finally had an answer.

  8. Katie Wright
    August 23, 2010 at 10:16 pm

    I had a normally developing child for 2 yrs. “I love you Mama,” “I wnat my brother,”when can I drive a car,” were phrases I heard w/ regularly. My son had pretend play and was very althletic. After horrific adverse vaccine reactions the son I knew was gone. No speech, no running, no eating, no sleeping, no recognizing me.

    Rajiv and Piper this may not be your experience- you are lucky if it isn’t. But please do not judge what you have not experienced first hand. BTW emerging envionmental research powerfully implicates over vaccination as a trigger for the regressive autim subgroup.

  9. sarah
    August 27, 2010 at 8:20 pm

    my son was born at 30 weeks and we knew that he would be neurologically different. we always had early intervention. i had all of his vaccines separated and given at different times. i don’t believe in the vaccine therory.
    we have many friends with children who are autistic and are of the mind that they were born that way. i think any research is helpful research. i think the phrase “a cure” should not be used. there is help but no cure, i have accepted that. so with that in mind we enjoy him for the wonderful child that he is now!

  10. August 29, 2010 at 1:03 am

    My son Luke, had Chromosone 15 Duplication 15 Syndrome and we picked this up as a result of him lacking meeting his milestones. (ie Head lag at six months, not rolling, or attempting to reach for toys out of his reach). We were offered genetic testing from 12months ans decided to wait to see how he progressed as he was a good eater and sleeper and very happy baby. So it is a very difficult issue. Once we knew that he had this condition, we had the MMR done as seperate injections. (Which is now not possible.) We just need parents to demand genetic testing for their children who are delayed in milestones. We never thought for ome minute we were going to have a special needs child.

    • Melinda
      November 15, 2011 at 12:30 pm

      My son has just been diagnosed with Chromosome 15 duplication. I was wondering how your son is doing. Have therapies helped him? Did you put him in AB Therapy? Is he autistic? Is he verbal? I have so many questions and would love to know what you have found that is successful and what was not.

  11. evelyn olive
    February 3, 2011 at 12:06 pm

    My neice and nephew both have microdeletion ch 15 disorder. Their deletion starts on 15q13.2 and goes into 13.3. They were Autistic at birth! My nephew is 10 and we didn’t know he had this deletion until October of 2010! He also has hypotonia, facial dysmorphism, hole in his heart, a benign tumor on his forehead, blind in left eye, deaf in right ear, and has hypohidrotic ectodermal dysplasia. My neice is 5 she also has Hypohidrotic ectodermal dysplasia, cerebral palsy, epilepsy, twisted stomach and esophagus, low average hearing, visually impaired. They both need a lot of help academically and receive speech therapy.
    I do not have a problem with the Autism Tissue Program. The kids will be signed up for the program this month. My worry is with the death rate. No one will give us an idea on life expectancy or what kind of things to look out for. I will not dwell on it just want to know in case there are things we can do to prevent it.

  12. May 27, 2011 at 5:08 pm

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  13. Trischa Lanum
    October 16, 2011 at 10:49 pm

    Our eight year old(adopted) son was recently diagnosed w/15q duplication by an Army geneticist. While not all children who are on the spectrum suffer from 15q, there are those of us who love children that do. While the knowledge of our sons genetic anomoly does not change our daily lives, we are anxious “connect the dots.” I have read all the books, I-searched many conflicting opinions, address our sons many characteristics(sensory integration, sleep disorders, mood dysregulation,seizures,learning and social/emotional delays) at his many specialty appointments and educational setting, BUT at the end of the day “answers” are illusive. Management is the way to go for our family. I don’t want to spend Matt’s life chasing the wind, at the expense of enjoying him for the time we have him …however long that is. I guess my point may have been lost in my rambling. For those who don’t have children w/ 15q, please don’t dismiss the importance of research because we are few in number. Those of us who parent children w/ASD have to make the choice whether we choose to immunize, eat gluteun free, etc. It’s important that we remeber our commonalities, not argue over the differences.

  1. August 21, 2010 at 8:46 pm

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