With no obvious culprit in sight,
geneticists do broader sweeps to identify
autism’s causes By Susan Gaidos
It’s a high-stakes version of the board game Clue. Scientist-detectives probing the origins of autism must contend with an enormous cast
of characters. Within the past year,
researchers have found dozens, possibly hundreds, of rare genetic mutations
that may contribute to the disorder, and
a handful of common mutations may also
be involved.
Faced with this staggering lineup of
genetic suspects, scientists have turned
to new DNA sequencing technologies
and other methods to track clues within
the brain and pin down the who, where
and how underlying autism.
Nobody expects to find Colonel Mustard in the kitchen with a knife. The latest
clues have made it clear that with autism,
there will turn out to be multiple culprits.
“There’s not going to be a simple
explanation for autism,” says neurogeneticist Daniel Geschwind of the University of California, Los Angeles. “The
genetics are very complex, and there are
likely to be many different genetic and
A boy diagnosed with autism makes eye
contact with a therapist while working
on his social and communication skills.
biological mechanisms involved.”
Researchers have long known that
genes play a role in autism, a disorder
marked by impaired social interaction
and communication. Studies of twins sug-
gest that as many as 90 percent of autism
cases may have a genetic link. The prob-
lem, in many cases, is that scientists don’t
know what to make of those findings.
“What you hope for is that you find a
mutation and then every time you see
the mutation, a person’s got some evidence of autism,” says Yale University
neurogeneticist Matthew State.
But that’s not what scientists see.
Studies have linked a handful of common
gene variants to autism, but most of the
genetic mutations implicated in the disorder are rare. In many cases, the mutations found in kids with autism are also
seen in kids without autism. And some
of the gene variants that raise the risk
of autism have also been linked to other
psychiatric disorders, such as manic-depressive illness or schizophrenia.
To try to untangle these complications, researchers are using the genetic
findings as a starting point, followed
up by studies to see how and where
the products of these potentially rogue
genes work in the brain. Lately a more
complete picture has begun to emerge.
“ What genetics is doing for us is telling
us where to look and what are the fundamental processes that are involved,”
State says.
Identifying common MOs
While it’s still early in the game, recent
findings tie many of the rare mutations
to genes in common biological pathways and net works — most of which help
control the way the brain develops and
functions. Some of the genes belong to
pathways used by brain cells to communicate, while others are involved in the
growth of nerve cells, anchoring cells
together or signaling within a cell.
Such findings provide targets for new
treatments and approaches, the scientists
