Autism/genetics... of interest to some here, perhaps?
lpacker
Duke Geneticists Unraveling The Tangled Web Of Autism
DURHAM, N.C. -- Less than three years after beginning a search for
genes that confer a risk of developing autism, Duke geneticist
Margaret Pericak-Vance and her colleagues have found evidence of two
defects that may be linked to the complex combination of behaviors
called autistic spectrum disorder.
Such behaviors include failure to make eye contact, social
withdrawal, lack of language, and repetitive behaviors such as
rocking or head banging. Doctors believe that the disorder begins
during development of the brain, possibly even before birth, and that
the change prevents affected people from properly processing sensory
information from their environment.
Pericak-Vance, director of the Duke Center for Human Genetics and
lead investigator of the autism genetic studies at Duke, and her team
located defects in tiny sections of chromosomes 15 and 7. And, for
the first time, they said they have evidence of a genetic mechanism
that hides the effect of some genes.
"You could say we have it narrowed down to a line-up of good
suspects, but we still can't finger the culprit until we get direct
evidence," Pericak-Vance said. "In this case, that most likely will
be more than one gene. It will probably include variations of many
genes that in combination interact to result in autistic behavior.
Those details will come with continued research of our suspect genes."
The research was supported by the Duke's Center for Human Genetics,
the National Alliance of Autism Research, and by grants from the
National Institutes of Health.
The collaborative group of scientists, which included researchers and
clinicians from Duke, the University of South Carolina, and Johns
Hopkins University, located and collected genetic information on more
than 100 families with at least two autistic children. By comparing
the genes from parents and siblings to the genes of autistic
children, the scientists were able to narrow their search to a few
small pieces of chromosomes, the carriers of genetic information.
Now, in a series of papers, some in press, the scientists report:
Confirmation that a small region of chromosome 15 is duplicated or
deleted in some autistic children. This area of chromosome 15 is
highly unstable and prone to genetic rearrangement. The region
includes genes for Prader-Willi Syndrome and Angelman syndrome, two
disorders which can manifest autistic-like behavior. (November 1999
issue of the journal Neurogenetics.)
Completion of a detailed genetic map of the chromosome 15 candidate
genes (Dec. 15, 1999 issue of the journal Genomics).
Discovery that this same area of chromosome 15 contains genes that
recognize a powerful chemical signal in the brain called GABA or
gamma aminobutyric acid. Pericak-Vance and her colleagues found
evidence that at least one form of autism is associated with a
genetic marker in the vicinity of a GABA receptor gene. (January 2000
issue of the American Journal of Medical Genetics)
Completion of a detailed genetic and behavioral study of a subset of
children with the chromosome 15 defect. The Duke researchers
concluded that autistic children with a particular genetic profile
may be a specific subtype that can be distinguished from other forms
of autism. These children all have two copies of the same small
region of chromosome 15, while people without autism only have one
copy per chromosome. (Neuropsychiatric Genetics, in press).
Confirmation that another genetic variation in chromosome 7 also
predisposes children to autism. The scientists said the findings
suggest that genes inherited from one parent may be masked during
development, a phenomenon called imprinting. (November 1999 issue of
Genomics).
Autism is a complex disease that affects 2-10 per 10,000 people,
making it the third most common developmental disability -- almost as
common as Down's syndrome. But because of the broad differences in
severity of the disease, doctors have difficulty diagnosing it with
certainty. Some children simply talk later than normal, while others
have severe withdrawal with self-destructive patterns of repetitive
head banging and difficulty sleeping. In the past, many parents
endured frustration and shame when told that their withdrawn, silent,
autistic child is a product of their own poor parenting. But the Duke
researchers are now demonstrating that autism is a complex genetic
syndrome that may actually turn out to be several related disorders,
each with its own individual treatment.
"One of the biggest difficulties has been coming up with a firm way
of diagnosing autism," said Dr. Michael Cuccaro, associate professor
of neuropsychiatry at the University of South Carolina, Columbia, and
a collaborator on the project. "There has never been any definitive
diagnosis beyond behavioral classifications. One major outcome that I
see to the genetic studies is a way to finally identify more
precisely who has autism. This information would be extremely useful
for families who are often confused with differing medical opinions."
For example, when the scientists looked at the children's behaviors,
they noticed a pattern of similar behaviors in some of the children.
Some had speech delay, lack of social skills, and "stereotyped" or
repetitive behaviors, that seemed to cluster in together with a
specific genetic defect. In addition, these children had seizures and
hypotonia, or low muscle tone, characteristics that are not normally
associated with autism. These children all had a duplication of part
of chromosome 15.
"We would like to be able to link subtypes of autism with more
specific intervention strategies," Cuccaro said. "For example, some
children may benefit more from medicines, some with behavioral
interventions, although many will need both."
In fact, scientists at Duke's Center for Human Genetics are teaming
with psychiatrists who treat patients with a variety of psychiatric
disorders to investigate the genetic component of mental illnesses.
"At this time, diagnosis of psychiatric disorders is as superficial
as, say, fever," said Dr. Ranga Krishnan, chairman of Duke's
department of psychiatry. "All we can say is the patient has a fever.
We are diagnosing based on a symptom. With the genetic approach, we
may be able to classify psychiatric disorders based on an underlying
genetic and biochemical cause, just as fever is now classified based
on what caused it, whether it be bacterial, viral, etc. This has
fundamental implications in that it could lead to a new and possibly
different classification of psychiatric disorders and new treatment
approaches that may be more specific."
The researchers began their quest to find genes associated with brain
abnormalities by using the same approach they used to find genes
associated with Alzheimer's disease and other neurological disorders.
They went to the source: families with more than one child diagnosed
with autism. By studying such families, the researchers can look in
detail at sections of chromosomes that are the same in affected
children. When they looked in detail at a section of chromosome 15 in
63 families with at least one autistic child, they found that the
autistic children had genetic abnormalities in this tiny region of
chromosome 15 that contains about 50 genes.
"Our studies, and those of others show that the genetic errors that
lead to autism are introduced when a piece of a chromosome breaks
apart and recombines during the formation of sperm and eggs," said
Pericak-Vance. "As a result some children with autism have an extra
copy of a piece of chromosome 15 and in some, the piece is missing.
We believe the gene or genes responsible for the behavioral changes
we see in some children with autism are located in this area of
chromosome 15."
The scientists aren't sure which of the genes in the region lead to
autistic behaviors, but they have identified a few strong candidates.
In the January 2000 issue of the American Journal of Medical
Genetics, Pericak-Vance and her colleagues made a careful genetic
analysis of the possibility that one of the three GABA receptor
subunit genes on chromosome 15 is linked to autism. They were not
able to definitively link the GABA genes to autism, but they were
able to say that at least one gene in the GABA region of chromosome
15 is associated with autism. The complex nature of autism makes it
difficult to single out any one gene, and in fact, more than one gene
may be involved, the researchers say.
"GABA is the major inhibitory neurotransmitter in the brain," said
John Gilbert, a researcher at Duke's Center for Human Genetics. "Any
change in the brain structures that recognize GABA could have
implications during brain development and function. It makes a nice
story if GABA turns out to be involved in autism, but we can't be
sure yet."
To that end, Gilbert, Pericak-Vance, Dr. Jeffery Vance and their
colleagues reported in the Dec. 15, 1999 issue of the journal
Genomics that they have completed a detailed genetic map of the area
of chromosome 15 that contains the suspected autism genes. The map is
a milestone that will help researchers mark off which genes are
definitely not involved and narrow down the list of candidate genes
until an affected gene or genes emerges.
In the November issue of the journal Genomics, the researchers
reported another potential genetic link to autism. This link is on
chromosome 7.
"Our results show that just as on chromosome 15, the region of
chromosome 7 suspected to be involved in autism is exceptionally
susceptible to breaking apart and recombining with its chromosome
pair. Apparently, in some cases this recombination goes awry and
parts of the chromosome are not duplicated faithfully. The result is
that a piece of chromosome 7 is inverted or turned upside-down with
respect to the rest of the chromosome in some cases of autism."
The researchers also found evidence of a genetic mechanism that hides
the effect of genes. One such mechanism is called imprinting, in
which genes inherited from one parent are "masked" during
development. Such a mechanism may be at work here, Pericak-Vance
said, since the area of chromosome 7 is known to have imprinted
genes. The same is true for the autism-associated region on
chromosome 15. Although the data is suggestive, the researchers have
no direct evidence yet that this is the case.
Currently, the Duke research team is making progress narrowing down
the potential candidate genes on chromosomes 7 and 15 by studying
additional families and by using their existing genetic maps and
genetic markers to test each potential gene candidate.
"I think there has always been some doubt, even until recently, that
this is truly a biological disease," said Cuccaro. "This will
hopefully be the science that puts to rest the idea that parenting
style contributes to the development of the disorder. We can say now
that autism is definitively a neurobiological disorder."
--
For info on TS, OCD, ADHD, rage, and much more:
http://www.tourettesyndrome.net
For the Special Education Advocacy Tutorial for parents:
http://www.tourettesyndrome.net/advocacy_selfhelp_intro.htm
jimsal
of the folks I work with has just been diagnosed with tourettes in addition
to his long standing autism diagnosis. anyway your pos is really
interesting. At last years autism confrence in Utah a researcher from Weber
state university gave a talk about genetic factors in autism. he talked
allot about Chromosome 15 and 7. Interestingly he said there were also
common genetic similarities between auto-immune deficiencies like some kinds
of arthritis and autism.
Jim
"lpacker" <lpa...@optonline.net> wrote in message
news:389dae8f....@news.erols.com...
Vivek Jaiswal
What is it that I can do?