There's been much excitement about the latest big genetic study into autism, published in Nature : the grandly titled Autism Genome Project, brought to you by a crack team of no fewer than 177 researchers.
For a good summary of the research take a look here, and for a longer account here. In a nutshell, the authors examined DNA from almost 1000 people with an autism spectrum disorder. They were looking for deletions and duplications of segments of DNA: so-called copy number variations (CNVs). A CNV could be anything from missing half a chromosome, down to having an extra copy of just a small part of a single gene.
It turned out that autistic cases carry more CNVs affecting genes, on average, than controls. The difference was small - just a 1.2-fold increase - but significant, and reassuringly, the extra CNVs were especially common in genes already known to be related to autism. The authors conclude that about 5% of cases of autism are likely caused by a single CNV of the type they studied. In almost all cases it was a different variant in a different gene - in other words, each case is genetically unique. Here's the gory details.
So we have new autism genes - dozens of them. But is that good news? Not really - with genes, it's not a case of the more the merrier. If there's just one gene for a disease, it's pretty easy to work out how it does it. Genes code for proteins. Proteins do stuff in cells. Follow the trail of causality from gene to protein to the impact on the body, and you've understood the disorder. Nowadays, with the help of modern genetics, you can do this in a few years.
There are several hundreds of these nice easy monogenetic diseases. For example, a few months ago I reported on a case report of a guy with complex neurological and psychiatric symptoms, caused by a single mutation in the gene for the enzyme sepiapterin reductase. All of his symptoms followed logically from that mutation. With autism, there are already many known genes; this study has found many more; more are implicated each year. Oh dear.
My suspicion is that a large proportion of all of the genes that control brain development - which is a lot - will turn out to be autism genes. The brain is amazingly complex. Thousands of genes work in synchrony build a "normal" brain. There are an awful lot of things that might not go according to plan.
Sometimes, the outcome is a rare and bizarre condition like holoprosencephaly. More often, the end result falls into one of a few common categories, like epilepsy and mental retardation (intellectual disability). There is no one gene for these disorders: they're just one of the things that happens when a gene goes wrong. I suspect that autism is another.
At present we have no clear idea what is different about autistic brains. If we did, we could probably predict which genes would be autism genes. For example, one theory of autism is that brain cells are too tightly packed. Suppose that's true (it's almost certainly not that simple), and suppose that one day, someone finds a gene, pushy, that causes developing brain cells to make little molecular spikes that push each other away. It would not take a genius to predict that a mutation that stops pushy working might cause autism.
Of course pushy mutations would only account for a small fraction of cases: plenty of other mutations would have the same eventual impact. The point is that if we understood the biology of autism in this way, we'd know which genes to look for; we wouldn't have to fish around the whole genome looking for all kinds of random mutations.
It's true, as the authors of the Nature paper say, that genes can themselves provide clues as to the nature of the disease. They present a neat diagram of the functional relationships between their autism genes - what they do inside cells. But this is painted with a very broad brush - "cell adhesion" i.e. how cells fit together; "central nervous system development"; "cell proliferation".
This is why I'm personally more interested in research into the psychology and the neuroscience of autism than I am by the genetics. Genetic studies are important but there are glaring gaps in our knowledge that probably deserve at least as much attention.
Just for starters, there have been very few studies simply comparing the brains of autistic people to non-autistic controls at autopsy. I think in total there have been published post mortem reports on maybe 30 or 40 autistic brains...ever. Some very interesting results have emerged, but with such small numbers it's impossible to know what's really going on, especially since most of the cases also suffered other conditions, such as - no surprise - epilepsy and mental retardation. We need more autistic people to donate their brains to science, and more scientists to study them.
Pinto, D. et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders Nature DOI: 10.1038/nature09146
