authorbio

Michael J. Dougherty, Ph.D., is Director = of=20 Education for the American Society of Human Genetics in Bethesda, = Mar...

m= ore=20 on author

The Genetics of Autism

Michael J. Dougherty

An ActionBioscience.org original article

=C2=BB= en=20 espa=C3=B1ol

articlehighlights

Research into cures for autism is difficult because the condition = is:

a genetic disorder, inherited from parents=20
linked to more than one mutated gene=20
affected by environmental factors=20
lacking genealogical data

re= ad=20 article
learn more
get involved
= educator resources

September 2000

=E2=80=9CLeslie Lemke gives virtuoso piano concerts despite = being blind,=20 palsied, and mildly retarded. After listening to an audience member = play or=20 sing a musical piece, familiar or not, Lemke cannot only reproduce it=20 perfectly (including any mistakes made by the challenger), but also = run it=20 through a set repertoire of different compositional=20 arrangements.=E2=80=9D¹

=E2=80=9CGiven any calendar date =E2=80=94 May 5, 1912 or = Christmas 8668 =E2=80=94 (John and=20 Michael) could instantly calculate the day of the week for that date, = even=20 taking leap years into = account.=E2=80=9D¹

Autistic savants exhibit incredible mental = ability.

=20

Deletion (1), duplication (2) and inversion (3) are all chromosome=20 abnormalities that have been implicated in autism. Illustrator: Richard = Wheeler=20 (Zephyris) 2007.

These incredible mental feats, like the toothpick counting and = phone-book=20 memorizing displayed by Raymond Babbit, Dustin Hoffman=E2=80=99s = character in the movie=20 Rainman, are characteristic of savant syndrome, a rare type of=20 brilliance sometimes associated with the mental disorder autism.

Autism affects the ability to lead a full, = independent=20 life.

Unfortunately, autistic savants, like the more common non-savant = sufferers of=20 autism, also possess characteristics of the disorder that make a full,=20 independent life nearly impossible. These debilitating characteristics, = which=20 become apparent in the first few years of life, include:

social detachment, e.g., failure to smile at parents and an = unawareness of=20 events around them=20
abnormal language development, such as repeating phrases in a = mechanical=20 voice=20
unusual repetitive movements, e.g., rocking and flicking fingers=20
mental retardation

Boys are four times more likely than girls to be = born=20 autistic.

Although savant syndrome is quite rare (only about 200 cases ever = recorded),=20 childhood autism is more common, affecting about one in 700 children. = Boys are=20 affected four times more often than girls. Despite this relatively high=20 frequency, scientists do not understand the mechanism of this serious=20 developmental problem. What they have discovered is that autism is one = of the=20 most heritable mental disorders known. In other words, autism appears to = be=20 largely genetic in origin, and most autistic children inherit the = disorder from=20 their parents.

Behavioral genetics changed the thinking about = the cause of=20 autism.

This is in sharp contrast to researchers=E2=80=99 earlier = explanations of the cause=20 of autism, which used to be attributed almost exclusively to = environmental=20 events, such as unemotional, indifferent parenting or brain damage. What = led to=20 such a dramatic change in thinking about the cause of autism? For the = most part,=20 it has been research in a field called behavioral genetics. Behavioral = genetics=20 seeks to explain differences in human behavior, including personality = traits and=20 cognitive ability as well as mental disorders, by finding the genes that = influence specific behaviors. At first glance, one might think that = genes have=20 no influence on personality or other behaviors, but rather, are the = result only=20 of conscious decisions.

More than just genes

A closer look at a well-understood example, however, suggests that = the causes=20 of behavior may be complex combinations of genetic and environmental = influences=20 =E2=80=94 that is, a mixture of nature and nurture:

Research has shown that genes and environment = influence=20 many behavioral conditions.

Children who inherit two copies of a mutated form of a single gene = on=20 chromosome 12 will be unable to break down the amino acid = phenylalanine, a=20 common component of food proteins.
If this deficiency, called phenylketonuria (PKU), goes undetected, = the=20 child will develop mental retardation, a condition with obvious = behavioral=20 consequences. Thus, a single gene can have profound effects on = behavior, in=20 this case by disrupting normal behavior.
Fortunately, a routine test conducted on every newborn in the = United States=20 can detect PKU shortly after birth, and a special diet that eliminates = phenylalanine can prevent retardation.

Reductionism is faulty because it looks at only = one element=20 of a disorder.

In the case of PKU, geneticists have determined that retardation = is due to=20 genetics (a mutated phenylalanine hydroxylase gene) and the = environment (a=20 phenylalanine-containing diet).

This simple example illustrates how reductionist thinking can be = misleading.=20 If we only focused on the gene, which we cannot change, we would miss = the=20 importance of the environment, which we can change.

No single gene accounts for behavior.

Investigating behavior

As it turns out, most behaviors are not linked to single genes = =E2=80=94 that is, the=20 patterns typical of Mendelian inheritance (such as the recessive = inheritance of=20 PKU) do not often arise in behavioral genetics studies. While a single = gene=20 cannot create normal behaviors, mutations in a single gene can disrupt = them.=20 This does not mean, however, that behavioral geneticists do not have = reliable=20 methods of investigating whether and how genes might influence behavior. = In=20 fact, families, adoption, and twinning offer natural experiments in = shared=20 inheritance that allow careful study of behaviors. For example:

Studies of twins show if and how genes influence=20 behavior.

Identical, or monozygotic twins, are genetically identical (i.e., = they are=20 clones).=20
If genetic factors influence a behavioral trait, identical twins = should be=20 more behaviorally similar than other relatives, for instance fraternal = twins,=20 who share only 50 percent of their genes.=20
Likewise, if genes influence behavior, family members, who share = from=20 one-eighth (first cousins) to one-half (siblings and = parents/offspring) of=20 their genes, should be more behaviorally similar than unrelated = people.=20

If one child is autistic, his sibling has a 3-6% = chance of=20 being autistic.

The lack of extended family histories makes it = difficult to=20 detect genes for autism.

Genes and autism

In the case of autism, the likelihood that the sibling of an affected = child=20 also would be affected is between three and six percent. This number is = small=20 enough that family doctors probably would never see enough cases of two = affected=20 siblings in the same family to suspect a genetic influence. Nonetheless, = this=20 incidence is about 100 times greater than the rate at which autism = affects=20 unrelated people in the population. Compounding the problems of rarity, = another=20 difficulty in detecting the genetic origins of autism is the lack of = family=20 pedigrees. Unlike people who inherit Huntington disease, a genetic = disease that=20 does not strike until after the affected person has reached reproductive = age,=20 persons affected with autism are so socially disabled that they never = marry and=20 have children. Thus, researchers do not have the extended family = histories that=20 have played such a critical role in the identification of genes = implicated in=20 cystic fibrosis, breast cancer, and other diseases.

Identical twins have a much greater probability = of being=20 autistic than fraternal twins.

Twin studies, however, have provided powerful evidence for the role = of=20 genetics in autism:

One study showed that the likelihood that the identical twin of an = autistic=20 child also would be autistic was 82 percent, whereas the equivalent = rate for=20 fraternal twins was only 10 percent.²
With sophisticated statistical techniques and numerous twin = studies,=20 behavioral geneticists now believe that as much as 90 percent of the=20 behavioral phenotype of autism is related to inherited=20 genes.²

Conclusion: Science needs to identify the genetic = contributors to autism.

Such a high genetic contribution appears to be the exception = rather than=20 the rule when considering complex behaviors. This is probably because = a=20 relatively small number of genes may be involved in autism (but = certainly more=20 than one), whereas other behaviors may be influenced by many genes. =

To identify the specific genes influencing autism, scientists = initiated an=20 international collaboration in 1996. As a result of this work and = further=20 studies, we someday may have a better understanding of the brain = differences=20 that lead to the bizarre and conflicting behaviors of persons who are=20 autistic.

=C2=A9 2000, American Institute of Biological = Sciences. Educators=20 have permission to reprint articles for classroom use; other users, = please=20 contact editor@actionbioscience.org for=20 reprint permission. See reprint=20 policy.

Michael J. Dougherty, Ph.D., is Director of = Education for=20 the American Society of Human Genetics in Bethesda, Maryland. He was = formerly=20 McGavacks of Loudoun Chair in Biochemistry and Associate Professor of = Biology at=20 Hampden-Sydney College in Virginia. His research and writing interests = include=20 yeast prions, protein structure, behavioral genetics, skeptical = thinking, and=20 the public understanding of science.
http://www.ashg.o= rg/press/mdougherty_bio.shtml=20

pri= nter=20 friendly format

The Genetics of Autism

learnmore links

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Pharmacogenetics

In another article on our site, Dr. Carol Isaacson Barash explains = how drugs=20 are being developed to treat genetic disorders.
http://www.a= ctionbioscience.org/genomic/barash.html=20

Nature and nurture

The article =E2=80=9CWhy teach bioethics?=E2=80=9D has an excellent = description of various=20 theories about the influence of nature and nurture on a child=E2=80=99s = development.=20
http://= www.actionbioscience.org/education/csongradi.html=20

Autism Society of America

Information about research, public awareness, parental support, and = advocacy.=20
http://www.autism-society.org/=20

Autism information

An all-encompassing site about autism. Includes the latest news in = research=20 and therapy. Lots of links to more online information.
http://www.autisminfo.com/i= ndex.html=20

Autismconnect

An international resource for the spectrum of autism disorders with = news,=20 discussion, and links offered. Also, you can subscribe to alerts on = various=20 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=20 science.
http://www.genome.gov/

Is biology a political science?

Discusses the relationship of science with our culture and the = importance of=20 not taking a reductionist approach toward science.
h= ttp://caliber.ucpress.net/doi/full/10.1525/bisi.1999.49.6.479=20

Issues in genetic research

Highlights the principle concerns in genetic research today, = reductionism is=20 discussed.
http://www.physics.ohio-state.edu/~wilkins/writing/A= ssign/topics/genetic-issues.html=20

Center for the Study of Autism

Lists a large number of links to other sites presenting background=20 information about autism spectrum disorders and autism support groups. A = good=20 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=20 autism. The second link takes you to their forum for the sharing of = information=20 by people whose lives are affected by learning disabilities.
http://www.learningdisab= ilities.org.uk/=20
http://www.connects.org.uk/ =

The Geek Syndrome

An article, by Steve Silberman, on the frequency of autism spectrum = disorders=20 =E2=80=94 particularly Asperger=E2=80=99s Syndrome in Silicon Valley, = California =E2=80=94 and its=20 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=20 University Press, 1998) clarifies the meaning of the term = =E2=80=9Cgenetic,=E2=80=9D shows how=20 molecular studies have affected genetics, and provides the necessary = background=20 to understand the debates over the Human Genome Project.

AutismToday

This information site has a large amount of articles to raise = awareness about=20 Austim Spectrum Disorders. The second link takes you to their = conferences page=20 where you can find an autism conference close to you.
http://www.autismtoday.com/ =
http://www.autismconferences.c= om/=20

getinvolved links

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references=20
= educator=20 resources
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Virtual speakers on autism

TalkAutism.org delivers presentations of autism related information = free to=20 the autism community or via professional continuing education online. =
http://www.talkautism.com/

The Frequency of Inherited Disorders Database

Knowing how the frequency of inherited diseases varies from place to = place is=20 essential for doctors and health care planners. Such information can = even reveal=20 patterns of human evolution and past migrations. This new database from = the=20 University of Wales gathers figures on the prevalence of more than 280 = inherited=20 disorders.
http://archive= .uwcm.ac.uk/uwcm/mg/fidd/index.html=20

Walk for Autism Research as a community

=E2=80=9CWalk F.A.R. for NAAR is the National Alliance for = Autism Research=E2=80=99s=20 signature event held annually in numerous communities throughout the = USA=E2=80=A6 Find=20 out how you can mobilize your community to raise awareness and = critically needed=20 funding for autism research.=E2=80=9D
http://www.autismspeaks.o= rg/index2.php=20

Autism Genetic Research Exchange (AGRE) family study

=E2=80=9CDoes your family have two or more siblings in the immediate = family affected=20 with autism, PDD, or Asperger=E2=80=99s Syndrome?=E2=80=9D asks AGRE. If = you do, you may want to=20 participate in their ongoing research in the U.S. to help them = =E2=80=9Cbetter=20 understand the differences between individuals with autism.=E2=80=9D The = second link=20 takes you to Cure Autism Now, the foundation which funds the AGRE study, = where=20 you will find additional ways in which to participate in finding a cure. =
http://www.familyagre.o= rg/participation/=20
http://www.cureautismnow.org/ =

articlereferences

learn=20 more=20
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Jack Maguire. (1990). Care and Feeding of the Brain. New = York:=20 Doubleday=20
Plomin, R. (ed.), DeFries, J., McClearn, G., and Rutter, M. = (1997).=20 Behavioral Genetics. New York: W.H. Freeman and Co. =

General References:

=C2=BB Bailey, J.M., Phillips, W., and Rutter, M. 1996. = =E2=80=9CAutism: Towards an=20 integration of clinical, genetic, neuropsychological, and = neurobiological=20 perspectives.=E2=80=9D Jour. of Child Psychology and = Psychiatry. 37:89-126.=20
=C2=BB Bailey, J.M., LeConteur, A., Gottesman, I.I., Bolton, P., = Simonoff, E.,=20 Yuzda, E., and Rutter, M. 1995. =E2=80=9CAutism as a strongly genetic = disorder:=20 Evidence from a British twin study.=E2=80=9D Psychological = Medicine,=20 25:63-77.

educatorresources

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ActionBioscience.org original lesson

This lesson has been written by a science educator to specifically = accompany=20 the above article. It includes article content and extension questions, = as well=20 as activity handouts for different grade levels.

Lesson Title: Autism: A Different World=20
Levels: high school - undergraduate=20
Summary: In this lesson, students gain a better=20 understanding of autism. Students can brainstorm resolutions to = hypothetical=20 scenarios involving autistic children, research the story of an = autistic=20 savant, consider if Mendel=E2=80=99s work has relevance to inherited = behavioral=20 problems=E2=80=A6 and more!

Download/view=20 lesson.
(To open the lesson=E2=80=99s PDF file, you = need Adobe = Acrobat=20 Reader free software.)

Lessons for middle school

The following links will take you to middle school lessons available = on other=20 web sites:

=C2=BB Movies are Us
This lesson on behavioral disorders = requires renting=20 one of five movies, including =E2=80=9CRainman=E2=80=9D about an = autistic savant.
http://faculty= .washington.edu/chudler/videos.html=20
=C2=BB Wearing My Genes: Basic Principles of Heredity
A = student activity=20 that examines heredity using a Punnett square and a few props. http://www.iit.edu/~smile/= bi9608.html=20

Useful links for educators

=C2=BB It Runs in the Family: Genes and Behavior (5/03) =
Science Friday=20 Kids=E2=80=99 Connection offers a program summary and audio of this = discussion radio=20 program, related links and resources, activities, and content = standards=20 correlation for the unit.
http://www= .sciencefriday.com/kids/sfkc20030502-1.html=20

Useful links for student research

In addition to the links in the =E2=80=9Clearn more=E2=80=9D section = above:

=C2=BB Behavioral Genetics
Description of this field and its = implications,=20 from the Human Genome Project.
http://www.ornl.gov/TechResources/Human_Genome/elsi/behavior.html=20
=C2=BB Online Mendelian Inheritance in Man (OMIM)
This = database is a=20 catalog of human genes and genetic disorders and contains textual = information,=20 pictures, and reference information. Run by the National Center for=20 Biotechnology Information at Johns Hopkins University.
http://www.ncbi.nlm.nih.gov/om= im/=20
=C2=BB Autism Glossary of Terms and Acronyms
Suitable for = medical reports=20 and research. Also check out their home page for links and articles. =
http://www.a= utism-resources.com/autismfaq-glos.html=20
=C2=BB Genetics Glossary with Illustrations
The National Human = Genome=20 Research Institute offers a glossary that you can read and listen to, = as well=20 as view definition-related illustrations:
-Talking Glossary of = Genetic=20 Terms (English) http://www.genome.gov/glossar= y.cfm=20
-Glosario de T=C3=A9rminos Gen=C3=A9ticos (en = espa=C3=B1ol/Spanish) http://www.genome.gov/sgloss= ary.cfm=20


biodiversity	environment	genomics	biotechnology	evolution	new = frontiers	educator=20 = resources