Autism-Genetic Link

  Science Daily — Using an innovative statistical approach, a research
team from Washington University School of Medicine in St. Louis and the
University of California, Los Angeles, has identified two regions of DNA
linked to autism. They found the suspicious DNA with a much smaller sample
of people than has been used traditionally in searches for autism genes.
     Autism -- a disorder that involves social deficits, language problems
and repetitive, stereotyped behaviors -- affects around one in 1,000
children. And the combined incidence of autism spectrum disorders, which
include Asperger syndrome and pervasive developmental disorder, brings the
total number of affected children to one in every 150 births. Boys are
affected three to four times more often than girls.
     There's clearly a genetic component to autism, according to John N.
Constantino, M.D., associate professor of psychiatry and pediatrics at
Washington University School of Medicine and a co-principal investigator on
this latest study. If one child in a family is autistic, there's a 10
percent chance a sibling also will have autism. Past research has isolated a
few regions of DNA linked to autism, but very few of those studies have been
replicated, so no specific autism genes have yet been identified.
     "Those older studies used what's called an 'affected sib pair' design
that looks for genetic markers in siblings with autism," says Constantino.
"That approach has worked well for single-gene disorders, but autism is a
complex disease that may involve many genes that each make very small
contributions. When that's the case, it's harder to find genetic markers."
     So Constantino's group, in collaboration with the other co-principal
investigator, Daniel H. Geschwind, M.D., Ph.D ., and neuropsychiatric and
genetics researchers at UCLA, is using a different approach. They report
their findings in the April issue of the American Journal of Psychiatry.
     "Although we once believed you either had this condition or you
didn't, we now know that there's a continuous distribution of autism
symptoms from very mild to very severe," Constantino says.
     That means in families where a child is autistic, parents and
unaffected siblings may have very subtle communication impairments or
behavioral tendencies that would be considered autistic only in their most
severe forms. Those traits may indicate genetic tendencies that contribute
to autism and now can be measured with a diagnostic interview tool called
the Social Responsiveness Scale (SRS), which Constantino developed with his
colleague Richard D. Todd, Ph.D., M.D., at Washington University.
     Using the SRS to gather data about both children with autism and their
unaffected parents and siblings allowed the researchers to take a more
quantitative approach to find subtle symptoms of autism that aggregate in
families. In all, they used the SRS to study members of 99 families who were
part of the Autism Genetic Resource Exchange (AGRE).
     "We characterized everyone using the quantitative measures that the
Social Responsiveness Scale provides," Constantino explains. "With the SRS,
we looked not just at whether a person has autism but more systematically at
the degree of autistic impairment. Then we analyzed their genetic material
and found significant linkage to these symptoms on regions of chromosomes 11
and 17."


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~Nate.