The autism spectrum disorders (ASDs), including autism and its milder cousin Asperger syndrome, affect about 1 in 150 American children. There’s a lot of evidence that these conditions have a strong genetic basis. For example, identical twins who share the same DNA are much more likely to both develop similar autistic disorders than non-identical twins, who only share half their DNA.
But the hunt for mutations that predispose people to autism has been long and fraught. By looking at families with a history of ASDs, geneticists have catalogued hundreds of genetic variants that are linked to the conditions, each differing from the standard sequence by a single ‘letter’. But all of these are rare. Until now, no one has discovered a variant that affects the risk of autism and is common in the general population. And with autistic people being so different from one another, finding such mutations seemed increasingly unlikely. Some studies have come tantalisingly close, narrowing down the search to specific parts of certain chromosomes, but they’ve all stopped short of actually pinning down individual variants.
This week, American scientists from over a dozen institutes have overcome this final hurdle. By looking all over the genomes of over 10,000 people, the team narrowed their search further and further until they found not one but six common genetic variants tied to ASDs. This sextet probably affects the activity of genes that connect nerve cells together in the developing human brain.
For any animal, it pays to be able to spot other animals in order to find mates and companions and to avoid predators. Fortunately, many animals move in a distinct way, combining great flexibility with the constraints of a rigid skeleton – that sets them apart from inanimate objects like speeding trains or flying balls. The ability to detect this “biological motion” is incredibly important. Chicks have it. Cats have it. Even two-day-old babies have it. But autistic children do not.
Ami Klim from Yale has found that two-year-old children with autism lack normal preferences for natural movements. This difference could explain many of the problems that they face in interacting with other people because the ability to perceive biological motion – from gestures to facial expressions – is very important for our social lives.
Indeed, the parts of the brain involved in spotting them overlap with those that are involved in understanding the expressions on people’s faces or noticing where they are looking. Even the sounds of human motion can activate parts of the brain that usually only fire in response to sights.
You can appreciate the importance of this “biological motion” by looking at “point-light” animations, where a few points of light placed at key joints can simulate a moving animal. Just fifteen dots can simulate a human walker. They can even depict someone male or female, happy or sad, nervous or relaxed. Movement is the key – any single frame looks like a random collection of dots but once they move in time, the brain amazingly extracts an image from them.
But Klim found that autistic children don’t have any inclination toward point-light animations depicting natural movement. Instead, they were attracted to those where sounds and movements were synchronised – a feature that normal children tend to ignore. Again, this may explain why autistic children tend to avoid looking at people’s eyes, preferring instead to focus on their mouths.
Alim created a series of point-light animations used the type of motion-capture technology used by special effects technicians and video game designers. He filmed adults playing children’s games like “peek-a-boo” and “pat-a-cake” and converted their bodies into mere spots of light. He then showed two animations side-by-side to 76 children, of whom 21 had autism, 16 were developing slowly but were not autistic, and 39 were developing normally.
Specific language impairment (SLI) is a language disorder that affects growing children, who find it inexplicably difficult to pick up the spoken language skills that their peers acquire so effortlessly. Autism is another (perhaps more familiar) developmental disorder and many autistic children also have problems in picking up normal speech and communication. These two conditions have a common theme of language difficulties running through them, but a new study reveals a deeper connection – both are linked to a gene called CNTNAP2.
The story of CNTNAP2 actually begins with another gene, whose name will be familiar to anyone with a passing interest in the genetics of language – FOXP2. Earlier this year, I wrote a long feature on the history of FOXP2 for New Scientist, but here’s a potted version.
FOXP2 was catapulted into the limelight earlier this decade when it became the first gene to be linked to an inherited language disorder. Initially heralded as “a language gene”, the hype surrounding FOXP2 was soon pierced by a number of studies which showed that the gene is an ancient one – it is present in a variety of different animals and has changed very little over the course of evolutionary time. In other species, it is hardly involved in language and in some, it isn’t even involved in communication.
The latest evidence suggests that FOXP2 affects the learning and production of complex sequences of movements. Such sequences are, of course, crucial for speech so it’s understandable that faults in FOXP2 leads to linguistic difficulties. So much for the hype, but the FOXP2 story isn’t over yet.
One of the most interesting things about it is that it’s a ‘transcription factor’, an executive gene that controls the activity of several subordinates. It was the quest to identify the genes that FOXP2 lords over that led to CNTNAP2. And lo and behold, it too plays a role in language.