Why Study Genes?

Past research hints at a link between autism and genes. For example:
When autism occurs in identical twins, both members of the set have
the condition 60 percent of the time. When autism occurs in fraternal
twins, both members of the set have the condition only 3-to-6 percent of the
time. Identical twins come from a single egg that splits in two, so they share
100 percent of their genes; fraternal twins come from two separate eggs, so
they are genetically different. If autism was not caused in part by genes,
then the number of identical twins with autism would not be any higher than the
number of fraternal twins with the condition. But, since both identical
twins have autism more often than both fraternal twins do, researchers
think that genes play a role in autism. (Folstein & Rutter 1977; Bailey et al
1995; Smalley et al 1988, as cited in Ingram 2000

http://www.nichd.nih.gov/publications/pubs/autism/factsheets/sub8.htm#Ref )
Family histories and family studies show that some of the
autism-like symptoms, such as delays in language development, occur more often in parents and adult brothers and sisters of people with autism, than in
families who have no autistic members or relatives. Because members of
the same family have similar gene sequences, these studies suggest that
something about gene sequences is linked to autism. Autism is a spectrum
disorder, meaning people with autism can have a range of symptoms. A
certain change in the gene sequence may make the condition very mild, so that a
person doesn't have autism, but has one of its symptoms instead. A
different change in that sequence could make the symptoms of autism more serious.
 
(Landa et al 1991; Landa et al 1992; Volkmar et al 1998; MacLean et al
1999 as cited in Ingram 2000
http://www.nichd.nih.gov/publications/pubs/autism/factsheets/sub8.htm#Ref)
Based on these findings, doctors have long felt that a link between
genes and autism was a strong possibility.
But researchers don't expect to find that just one gene causes
autism. Because of differences in peoples' symptoms, researchers believe that
autism is the result of many genes interacting with each other. At this point, it
seems that some children are born with a genetic susceptibility to autism.
What makes some susceptible individuals develop autism and others not is
an important research question.
 
What have CPEA researchers found by studying genes and autism?
Genetic studies of autism conducted by the CPEA Network
http://www.nichd.nih.gov/autism/cpea.cfm/ highlight some of the ways genes
may be involved in autism.

Chromosomes where defective genes are likely to be found
CPEA investigators, working with researchers from around the world,
are using a process called linkage analysis to identify genetic
"hotspots," or chromosome areas where defective genes related to autism may be found. So far the most promising leads seem to be on Chromosome 7, where genes for other language disorders are known to exist, and Chromosome 15 where genes or other developmental disorders have already been identified.

A missing piece of a chromosome could be tied to autism
A group of researchers at the University of California, Irvine,
found that one of their seven-year-old patients with autism was missing a
certain section of Chromosome 15 (Smith 2000

http://www.nichd.nih.gov/publications/pubs/autism/factsheets/sub8.htm#Ref).
Why is this such a great discovery? It's important because this is one of
the first times that a specific genetic problem has actually been found in
a person with autism.
 
In the past, studies looked at groups of people with autism and some
of the more general features of their genes, like which chromosomes might
have problem genes, and whether they had one, two, or three copies of a
chromosome. But in this study, researchers looked at one person at a time,
to carefully focus on that person's genes. This slow and complex process
allowed researchers to create a detailed catalog of all 46 chromosomes for
each autistic person, to find any missing blocks of these chromosomes.
After taking a close look at the autistic boy's chromosomes, the
scientists found that he was missing nearly 1,000 pieces of the genetic
sequence on Chromosome 15. Missing pieces of chromosomes mean that some of
the instructions for building the body or mind are missing. Without
these instructions, the body or mind may not be built correctly.
Using this discovery, scientists will try to match the missing chromosome piece to some of the genes they think play a role in autism. If they can match a gene to the missing section of the chromosome, they may be able to uncover how the gene changes the body to cause autism. These findings may also lead to treatments that correct the changes caused by the missing chromosome piece.

A genetic change found in many patients with autism
Researchers at the University of Rochester School of Medicine and
Dentistry in Rochester, New York, found that nearly 40 percent of people
with autism in their study had a change in their gene linkage that could
be a factor in causing their autism (Ingram 2000
http://www.nichd.nih.gov/publications/pubs/autism/factsheets/sub8.htm).
The sequence or pattern of your genes controls how your body builds its parts.
An alteration in that sequence changes how your body and mind are built,
which may lead to autism.
Specifically, 39 percent of the people with autism in the study had
a change in one of the two copies of the HOXA1 gene
http://www.nichd.nih.gov/publications/pubs/autism/factsheets/sub5.htm,
which is located on Chromosome 7. (Remember that chromosomes come in pairs,
which means your cells have two copies of every gene.) The percentage of people
who had the change in one of their genes, but did not have autism and were
not related to anyone with autism, was much lower (only 22 percent).
 
Because twice as many people with autism had the gene change when compared with people who did not have autism but had the gene change, the HOXA1 gene
could play a role in causing autism.

In addition, 33 percent of people in the study, who did not have
autism, but were related to someone with autism, also had the change in
their gene, which supports the idea that the HOXA1 gene plays a role in
causing autism. These findings suggest that the genetic sequence of these
families is linked to autism and autism-like symptoms in some way.
Scientists need to do more studies to find out just what that link is.
But scientists don't think that the change in the HOXA1 gene by
itself causes autism. If the gene change was the only cause, then everyone who
had that change would be diagnosed with autism. Because this is not the case,
scientists think that the HOXA1 gene is only one of many genes that may
contribute to the autism.
 
What does the future hold for studies of genes and autism?
The CPEA Network is looking at other genetic mechanisms that may
account for why different genetic defects related to autism seem to be
found across different studies. Researchers in the Network will share their
information and their methods to see if other researchers get the same
results in other people with autism. Having several scientists get the
same results "confirms" that discovery. They will see if these and other new
genetic findings can be "replicated" or confirmed in other persons with
autism. Once confirmed, a discovery becomes the stepping stone to other
discoveries. Researchers in the Network hope that the latest findings on
genes and autism are just the beginning. By understanding both genetic and
environmental causes of autism, scientists may be able to understand how
to treat it and maybe even how to prevent it.
 
While some researchers focus on confirming the findings reported
here, other researchers are doing their own studies on different features of
autism and genes. Doctors and scientists will keep looking at genes and
environment and how they interact with each other until they solve the
mysteries of autism.

Where can I go for more information about autism?
The NICHD Clearinghouse provides information on autism and autism
research, and on other topics related to the health of children, adults,
and families. The information specialists at the NICHD Clearinghouse are
available at Email: NICHDClearinghouse@mail.nih.gov

References
Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, and
Rodier PM. Discovery of allelic variants of HOXA1 and HOXB1: genetic
susceptibility to autism spectrum disorders. Teratology, 62:393-405, 2000.
Smith M, Filipek PA, Wu C, Bocian M, Hakim S, Modahl C, and Spence
MA.
Analysis of a 1-megabase deletion i9n 15q22-q23 in an autistic patient:
identification of candidate genes for autism and of homologous DNA
segments
in 15q22-q23 and 15q11-q13. American Journal of Medical Genetics
(Neuropsychiatric Genetics), 96:765-770, 2000.

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