September 2000

“Leslie Lemke gives virtuoso piano concerts despite being blind, palsied, and mildly retarded. After listening to an audience member play or sing a musical piece, familiar or not, Lemke cannot only reproduce it perfectly (including any mistakes made by the challenger), but also run it through a set repertoire of different compositional arrangements.”¹

“Given any calendar date — May 5, 1912 or Christmas 8668 — (John and Michael) could instantly calculate the day of the week for that date, even taking leap years into account.”¹

These incredible mental feats, like the toothpick counting and phone-book memorizing displayed by Raymond Babbit, Dustin Hoffman’s character in the movie Rainman, are characteristic of savant syndrome, a rare type of brilliance sometimes associated with the mental disorder autism.

Unfortunately, autistic savants, like the more common non-savant sufferers of autism, also possess characteristics of the disorder that make a full, independent life nearly impossible. These debilitating characteristics, which become apparent in the first few years of life, include:

• social detachment, e.g., failure to smile at parents and an unawareness of events around them
• abnormal language development, such as repeating phrases in a mechanical voice
• unusual repetitive movements, e.g., rocking and flicking fingers
• mental retardation

Although savant syndrome is quite rare (only about 200 cases ever recorded), childhood autism is more common, affecting about one in 700 children. Boys are affected four times more often than girls. Despite this relatively high frequency, scientists do not understand the mechanism of this serious developmental problem. What they have discovered is that autism is one of the most heritable mental disorders known. In other words, autism appears to be largely genetic in origin, and most autistic children inherit the disorder from their parents.

This is in sharp contrast to researchers’ earlier explanations of the cause of autism, which used to be attributed almost exclusively to environmental events, such as unemotional, indifferent parenting or brain damage. What led to such a dramatic change in thinking about the cause of autism? For the most part, it has been research in a field called behavioral genetics. Behavioral genetics seeks to explain differences in human behavior, including personality traits and cognitive ability as well as mental disorders, by finding the genes that influence specific behaviors. At first glance, one might think that genes have no influence on personality or other behaviors, but rather, are the result only of conscious decisions.

More than just genes

A closer look at a well-understood example, however, suggests that the causes of behavior may be complex combinations of genetic and environmental influences — that is, a mixture of nature and nurture:

• Children who inherit two copies of a mutated form of a single gene on chromosome 12 will be unable to break down the amino acid phenylalanine, a common component of food proteins.

• If this deficiency, called phenylketonuria (PKU), goes undetected, the child will develop mental retardation, a condition with obvious behavioral consequences. Thus, a single gene can have profound effects on behavior, in this case by disrupting normal behavior.

• Fortunately, a routine test conducted on every newborn in the United States can detect PKU shortly after birth, and a special diet that eliminates phenylalanine can prevent retardation.

• In the case of PKU, geneticists have determined that retardation is due to genetics (a mutated phenylalanine hydroxylase gene) and the environment (a phenylalanine-containing diet).

This simple example illustrates how reductionist thinking can be misleading. If we only focused on the gene, which we cannot change, we would miss the importance of the environment, which we can change.

Investigating behavior

As it turns out, most behaviors are not linked to single genes — that is, the patterns typical of Mendelian inheritance (such as the recessive inheritance of PKU) do not often arise in behavioral genetics studies. While a single gene cannot create normal behaviors, mutations in a single gene can disrupt them. This does not mean, however, that behavioral geneticists do not have reliable methods of investigating whether and how genes might influence behavior. In fact, families, adoption, and twinning offer natural experiments in shared inheritance that allow careful study of behaviors. For example:

• Identical, or monozygotic twins, are genetically identical (i.e., they are clones).
• If genetic factors influence a behavioral trait, identical twins should be more behaviorally similar than other relatives, for instance fraternal twins, who share only 50 percent of their genes.
• Likewise, if genes influence behavior, family members, who share from one-eighth (first cousins) to one-half (siblings and parents/offspring) of their genes, should be more behaviorally similar than unrelated people.

Genes and autism

In the case of autism, the likelihood that the sibling of an affected child also would be affected is between three and six percent. This number is small enough that family doctors probably would never see enough cases of two affected siblings in the same family to suspect a genetic influence. Nonetheless, this incidence is about 100 times greater than the rate at which autism affects unrelated people in the population. Compounding the problems of rarity, another difficulty in detecting the genetic origins of autism is the lack of family pedigrees. Unlike people who inherit Huntington disease, a genetic disease that does not strike until after the affected person has reached reproductive age, persons affected with autism are so socially disabled that they never marry and have children. Thus, researchers do not have the extended family histories that have played such a critical role in the identification of genes implicated in cystic fibrosis, breast cancer, and other diseases.

Twin studies, however, have provided powerful evidence for the role of genetics in autism:

• One study showed that the likelihood that the identical twin of an autistic child also would be autistic was 82 percent, whereas the equivalent rate for fraternal twins was only 10 percent.²

• With sophisticated statistical techniques and numerous twin studies, behavioral geneticists now believe that as much as 90 percent of the behavioral phenotype of autism is related to inherited genes.²

• Such a high genetic contribution appears to be the exception rather than the rule when considering complex behaviors. This is probably because a relatively small number of genes may be involved in autism (but certainly more than one), whereas other behaviors may be influenced by many genes.

To identify the specific genes influencing autism, scientists initiated an international collaboration in 1996. As a result of this work and further studies, we someday may have a better understanding of the brain differences that lead to the bizarre and conflicting behaviors of persons who are autistic.

© 2000, American Institute of Biological Sciences. Educators have permission to reprint articles for classroom use; other users, please contact editor@actionbioscience.org for reprint permission. See reprint policy.

The Genetics of Autism

Pharmacogenetics

In another article on our site, Dr. Carol Isaacson Barash explains how drugs are being developed to treat genetic disorders.
http://www.actionbioscience.org/genomic/barash.html

Nature and nurture

The article “Why teach bioethics?” has an excellent description of various theories about the influence of nature and nurture on a child’s development.
http://www.actionbioscience.org/education/csongradi.html

Autism Society of America

Information about research, public awareness, parental support, and advocacy.
http://www.autism-society.org/

Autism information

An up-to-date site that includes the latest news in research and therapy. Lots of links to more online information.
http://www.ninds.nih.gov/disorders/autism/autism.htm

Autismconnect

An international resource for the spectrum of autism disorders with news, discussion, and links offered. Also, you can subscribe to alerts on various topics related to autism.
http://www.autismconnect.org

National Human Genome Research Institute

For a broad array of information about the implications of human genetic science.
http://www.genome.gov/

Issues in genetic research

Highlights the principle concerns in genetic research today, reductionism is discussed.
http://www.physics.ohio-state.edu/~wilkins/writing/Assign/topics/genetic-issues.html

Center for the Study of Autism

Lists a large number of links to other sites presenting background information about autism spectrum disorders and autism support groups. A good starting place for web-based research. http://www.autismwebsite.com/

Foundation for People with Learning Disabilities (U.K.)

Information, news, lists of organizations, and links on the topic, including autism. The second link takes you to their forum for the sharing of information by people whose lives are affected by learning disabilities.
http://www.learningdisabilities.org.uk
http://www.connects.org.uk

The Geek Syndrome

An article, by Steve Silberman, on the frequency of autism spectrum disorders — particularly Asperger’s Syndrome in Silicon Valley, California — and its implications.
http://www.wired.com/wired/archive/9.12/aspergers_pr.html

Read a book

Genetics and Reductionism by Sahotra Sarkar (New York, NY: Cambridge University Press, 1998) clarifies the meaning of the term “genetic,” shows how molecular studies have affected genetics, and provides the necessary background to understand the debates over the Human Genome Project.

AutismToday

This information site has a large amount of articles to raise awareness about Austim Spectrum Disorders. The second link takes you to their conferences page where you can find an autism conference close to you.
http://www.autismtoday.com
http://www.autismconferences.com/

Virtual speakers on autism

TalkAutism.org delivers presentations of autism related information free to the autism community or via professional continuing education online.
http://www.talkautism.com/

Walk for Autism Research as a community

“Walk F.A.R. for NAAR is the National Alliance for Autism Research’s signature event held annually in numerous communities throughout the USA… Find out how you can mobilize your community to raise awareness and critically needed funding for autism research.”
http://www.autismspeaks.org/index2.php

Autism Genetic Research Exchange (AGRE) family study

“Does your family have two or more siblings in the immediate family affected with autism, PDD, or Asperger’s Syndrome?” asks AGRE. If you do, you may want to participate in their ongoing research in the U.S. to help them “better understand the differences between individuals with autism.” The second link takes you to Cure Autism Now, the foundation which funds the AGRE study, where you will find additional ways in which to participate in finding a cure.
http://www.familyagre.org/participation/
http://www.cureautismnow.org/