Autism & Genetics

epigene-150x150When you research Autism Spectrum Disorders, you will quickly come to realise that there are as many theories on causes as there are researchers looking for answers. One fundamental aspect does seem to be completely undeniable however; there is a link to our genes.

This may seem counter intuitive to many people, who find themselves as parents to a child on the Autistic Spectrum, and that is quite understandable. After all, many parents have very limited, if any experience of Autism within their families, so how do we justify the genetic argument?

You may remember that back in 2003 that there was a huge buzz around The Human Genome Project. For the first time, scientists had mapped the human genome down to the last chromosome, and some serious work could begin, work which would revolutionize out understanding of our selves. Politicians hailed this breakthrough as potentially one of the most important scientific advances since Antibiotics and scientists around the world received a great deal of funding to carry on this important work. Then everything seemingly went quiet.

Genes, it turns out are quite complicated things. Your average bacterial cell has around 3200 genes. Yeast and other fungi have around 6000. The Fruit Fly, somewhere in the region of 13,000. A plant has around 25,000, while your average fruit has nearly 30,000. The Human Genome Project revealed something quite surprising. Human beings have around 21,000 genes contained within their DNA. This simple fact surprised a lot of people, and forced geneticists around the world to rethink a lot of what they took for granted.

The genome is very much more than what we thought, even just a few years ago. Indeed it turns out that our genetics are an extraordinarily dynamic adaptive system. Traditionally geneticists thought of our DNA as a kind of blueprint that pretty much dictates what our characteristics will be from the beginning of our lives to the end, with some genes being turned on, many others being turned off (we no longer need a tail for example).

It turns out these ideas are very much an oversimplifcation however, and largely as a result of The Human Genome Project, a new field in genetic research has emerged: Epigenetics.

After conception, a remarkable process begins, which determines which genes from our parents are going to be read by our developing cells and which are going to be ignored. Essentially the genes that are to be ignored are chemically imprisoned.

It has emerged, that many genes can switch on and off, very quickly and can be turned on as a response to external factors, such as the environment. Genes can be activated or deactivated temporarily or permanently. A good example of this is when we begin to regularly exercise. Suddenly genes activate which allow us to process sugars more efficiently, which has the benefit of making muscle fibres work more efficiently. If we cease this type or regime, these genes deactivate again.

When our bodies are exposed to toxins, diseases or foreign bodies, again previously dormant genes activate to help make cell repair and replacement more efficient.

Perhaps the most fascinating aspect of Epigenetics appears to be that these temporary changes can be hereditary, even while being only temporarily active. Studies performed in Sweden have found that in a remote and isolated village called Norrbotten, starvation due to instances of famine and crop failure went on to have detrimental health effects on at least two preceding generations, despite having plenty of food, almost as if these children’s bodies were trying to adapt in the same way as their parents or grandparents bodies had to, despite now having ample food. These kinds of quick single generational adaptions makes perfect sense in terms of evolution. It allows you to pass on genetic changes to your children in order for them to be better prepared for the environment you live in.

We are just gaining our first glimpses into how this incredibly adaptive mechanism works, and what happens if and when it malfunctions and perhaps how it is reacting to the very complex  environment, we as human beings inhabit. The thing that is becoming clear is just how dynamic and adaptive our genetics can be. Obviously we inherit many genetic traits from our parents, but it is now evident that the environment we live in, the environment our parents and grandparents lived in, the things and even experiences we or they were exposed to in every day life can also have an impact in how we and future generations develop.

The two things I am most commonly asked are: Where does Autism come from? and Why is it on the rise?

Family Genetics ASDAutism related conditions have probably been around as long as we have. It doesn’t take much research to spot historical figures who certainly appeared to have some of the more common traits. That being the case, there have probably always been many people who have carried some genetic predisposition toward Autistic Spectrum Disorders of one kind or another, but those genes until recently have only occasionally been expressed. Most researchers agree that combinations of genetic & environmental factors are playing a role in this recent rise in people on the Autistic Spectrum, and it is almost certain that some form of epigenetic mechanism is a part of that puzzle. It could be lifestyle, it could be pollution or toxins. It could even be evolution experimenting.

Currently The Human Genome Project is collecting most data, in order to compare the full genetic makeup of as diverse a group of people as possible in order to identify the specific genetic functions. This is research that will certainly be going on for the rest of our lives. Despite the silence in the media, this project is benefiting people already, specifically in the study of cancer. Perhaps in time, the exact nature of developmental disorders such as those on the Autistic Spectrum will become clear.

Genetic Differences – The Autistic Brain

Joseph Buxbaum PHD
Joseph Buxbaum PHD

A fascinating project conducted be a team of US molecular geneticists based at Mount Sinai and led by professor Joseph Buxbaum have been mapping the genome of autistic people.

The researched involved 810 volunteers – 60% of which had been formally diagnosed with ASD, with the remaining 40% neurotypical.

The research showed that the autistic group tended to have a very specific group of missing genes.

A simple, but important fact about genetics, is that genes can be switched on and off, but they can also be deleted. This isn’t an uncommon occurence, in fact everyone has certain genes which are deleted, that is the reason we all look different, or may look more like one parent, rather than another. Even twins can have deleted genes, leading to one twin being genetically predisposed to an illness or genetic condition that the other is not.

The genes that were noticeably absent in the autistic group were among many genes that control a  biological system called Autophagy; a complicated system which deals with programmed cell death and cell replacement and repair.

It has long been thought that Autophagy is important in brain development. During the early years of our development an almost countless number of synapses are formed, allowing the developing brain to learn, experiment and improve. All of these connections are created and controlled through the process of Autophagy – and as many of these connections prove to be useless, they are destroyed by the same process. Professor Buxbaum’s team suggest that these deleted genes lead to a system were perhaps not enough of these connections are removed, leading to a brain which is essentially “mis-wired”.

Genetics is a very complicated science and has been proven much more so in the last 20 years. While Professor Buxbaum’s research is not conclusive, it does seem to be following the pattern that there may not be a single defining cause of Autistic Spectrum Disorders, but rather a much more subtle system at play, were genetics, our environment, and even the environment of our ancestors can have a profound affect on whether autism occurs in a child or not.

Zen X

http://www.mountsinai.org/about-us/newsroom/press-releases/genetic-analysis-of-individuals-with-autism-finds-gene-deletions