Seeds of Autism. Not the mysterious condition it used to be. New tools made possible by the human genome project are revealing its genetic nature.
Autism can exist as a broad spectrum of symptoms, some severe and some mild. Many functional adults are working in intense professions, such as medicine, and have difficulty making person to person eye contact; a relatively minor form of an autistic disorder. Some persons from a very young age are more profoundly affected and unable to interact with other people or their surroundings. This condition has alarmed our modern society as it became more well defined and more often diagnosed in children. An unfortunate set of statements by a UK physician over two decades ago speculated that some immunizations might be linked to the condition. This turned out to be theory and conjecture that was not derived from actual scientific study, but this theory has unfortunately taken off and sparked much controversy. Indeed, many families that avoid immunization programs will cite this theory as the the basis for their decision. I can certainly understand their concern, but should you worry about immunizations regarding autism?
While my Family participates in childhood immunizations, we have many friends that do not, and they all worry about autism. For a time, without actual studies completed, it was not possible to convince those who support the immunization theory to the contrary. However, many studies have now been completed over the last decade make it clear that the incidence of autism is not higher in populations of school age children that are immunized compared to those that are not immunized. Both groups of children have the same incidence of autism.
In young children, indications of autism tend to occur just after the start of some common immunization schedules, and there is an understandable tendency to wonder about immunization. However, autism in non-immunized children also manifests itself at the same time. Developmentally, our babies and toddlers gain specific cognitive skills over several years; not all at once. Our children gain abilities to focus and follow objects visually, the ability to stand, and then walk. The ability to verbalize and signal in different ways and the development of speech and communication. Failures to gain these abilities are not known until the age of their expected appearance has passed.
Without any known genetic defects present in the parents, again there is tendency to blame immunizations, or something outside of the parent’s control. However, genetic defects can remain unknown simply because we have not looked for them. Fortunately the human genome project has provide the tools required to address the mystery behind Autism and begin to reveal the biochemical basis for these conditions. Finding genetic reasons that may be linked to autism was not easy to do in the 80‘s and 90‘s. Why? For one thing, we did not even know how many genes make up our Human Genome, and we only knew about several hundred genes in any kind of detail at all. Not only that, but the relative locations of genes we knew about was just that : relative. We knew the locations of a few thousand genes relative to each other on their resident chromosome, but we did not know the amount of DNA sequence or even the amount of other genes in between them.
With that relatively small amount of genetic knowledge, finding possible gene changes that might cause autism was like asking someone to fix an engine without any list of parts or any kind of reference guide. Finding the gene of interest was hard. Since 2000, we obtained the first drafts of the Human Genome, and science finally had a measured estimate on simply how many genes we have. Surprisingly, we Humans have about 22,000 genes. Impressive compared to the tiny Arabidopsis plant (15,000 genes), but not so impressive compared to Maize (Corn) which has over 100,000 genes!
Our genome comprises over 3-billion bases of DNA sequence, from each of our Parents. Sifting through a total of 6-billion bases of DNA sequence to look for small changes in sequence is a big job and one that was not possible just a few years ago. The human genome data, our DNA sequence, has made it possible to start looking for previously unknown genetic changes that are associated with Autism. That is exactly what large research projects have pursued in the last few years. NIH (USA) and MRC (UK) funds have supported studies to ask if genetic changes or mutations are present in children with autism.
In the last couple of years some examples of genetic defects in specific genes have been found in some families where the condition is frequently inherited. Interestingly these genes code for proteins that are known to have important roles in communication between neurons present in the brain. Thus, mutations (changes in DNA sequence) that alter their normal structure and function have effects in the developing and adult brain.
Most Autism, however, was still not explained by the genetic mutations in Families with clearly inherited Autism. Genome science has now begun to solve this mystery as well. Recently, in the journal Nature, a large study was reported that sought genetic changes in Autistic children, which may or may not be present in their Parent’s DNA. Over 60 centers participated in this large research program, from 12 different countries. Over 900 children were involved, with Autism spectrum disorders, and their Families had only one affected child.
Results have uncovered new DNA sequence differences that were already present in their Parent’s DNA, and thus inherited from their Parents. Surprisingly, some children also had DNA alterations that were not present in their Parent’s genomes. These later DNA sequence changes, sometimes DNA deletions, have occurred in the Mother’s DNA (egg) or Father’s DNA (sperm) during the process of fertilization. The single cell embryo divides to produce all the cells that make up our adult body, thus all cells in the child carry the genetic change. This means, without doubt, that these genetic changes have occurred early, even before birth or immunizations. That is the only way they can be copied in every single cell of the body.
In 2011, we are now learning that Autism spectrum conditions do indeed have a genetic cause. Finding the genes that are altered is the first step to provide the knowledge we need to understand why these changes alter normal neuron and brain function. We also now understand that many genetic changes in humans are created new, often during fertilization. This will be true for other genetic conditions, and not just Autism. Using the links below, you can read more about the large genomic study reported in Nature (from UCLA) and also about genes that are changed in some Autism, which encode proteins required for forming synaptic connections between neurons in our brains (from Tufts University).
Researchers link the APC Protein to Autism (from Tufts)
Many scientists and physicians have carried out studies, some lasting several years, to compare non-immunized children to immunized children, and to sequence the genomes of children and their parents. These have provided us with some very important answers. One should appreciate that these studies are typically funded by our government (Department of Health and Human Services) so we can get these answers. No one else gets these answers otherwise. The answers give us the power to address challenges such as autism. Where we could only speculate before, answers guide the next step: to develop ways to treat conditions such as autism.
It is already looking like more than one gene can be “hit” to predispose our children to developing an autism spectrum disorder. Neurons have many kinds of ion-channels, or example, to function fully. Thus, we should not be surprised that there will not be ONE gene harmed in the same way for every child with autism. This is the same for diseases I study (retinal degenerations). Different mutations in many different genes cause photoreceptor cells to die in patients with Retinitis Pigmentosa. The cells ultimately perish, but the reasons for this within the cell are different between individual RP Families. These differences often mean that a different approach will be required to treat each variation. Indeed a specific treatment strategy can help one patient but actually make the disease worst in another. Different people will likely require different kinds of autism therapy for the same reason.
Whether the treatment is a drug, gene therapy or working with an educational and learning therapist, one treatment will not fit everyone. With continuing research, a diagnosis which is identified with a specific gene will be useful to select a custom therapy for each patient and minimize the need to guess. Parents will then be able to start the best therapy as early as possible and not waist time on therapies that are not useful.