The specific area on chromosome 15 that impacts Autism is known as 15q11-13. This particular region will be duplicated and as a result may be linked to Autism. In fact, according to SFARI, the duplication on chromosome 15 is only the second most common large genetic alteration, chromosome 16 is the first. This duplication will impact approximately 1 in 500 children referred for genetic testing for developmental or intellectual delay and Autism. In fact scientists believe that this duplication is prevalent in as many as 1 in 12,000 people, typically developing or not.
In 2012 SFARI published an article based on a study found in Molecular Psychiatry, This study made up of 31,516 individual cases found two things. First, the duplication of 15q in control subjects was rarely found, and it also identified two types of chromosome 15 duplications linked to Autism. First, an interstitial duplication within the chromosome, and second an isodicentric duplication of the region which made up a completely extra chromosome.
So what did I just say? From what I can understand, an interstitial duplication is like a bow tie within the gene. The knot created, cuts away the genetic information that would have gone there and instead both ends of the bow tie copy each other, creating the duplication. According to 2013 SFARI article this type of duplication is very rare. Usually children carrying interstitial duplications have milder symptoms than those with an isodicentric duplication, making identification harder. A study done by the University of Tennessee Health and Science Center included 14 children with a known interstitial duplication. This is the largest known study of this type, because it is so rare. They found that the duplication was a result of genes passed down from the mother in 10 out of 14 of these cases. Nine of the 10 children have Autism. Four children involved in this study had this genetic duplication that came from the father and only two of those had Autism. Usually, as far as genetics are concerned, deletions and duplications in Autism are linked to the father and sometimes lead to the disorder. This was not the prevalent finding of this research team.
Isodicentric duplications, also known on chromosome 15 as Idic(15), are also rare and are a duplication of the gene. Common features of Idic(15), or isodicentric duplications, include hypotonia, seizures, and developmental delay, hence Autism.
In 2011 a group called Dup15q
Alliance launched a patient
registry which now contains approximately 243 families. Parents enter the
results of genetic tests, which are verified by a genetic counselor, and then
answer a questionnaire. Based on this it was found that approximately 41% of
children in this registry have Autism and approximately 17% have PDD-NOS.
Approximately half of the registry suffers from seizures, frequent ear
infections and approximately 83% have high pain tolerance.
Again in 2013 SFARI published an article about
duplications of chromosome 15. This article based on research presented at the
Dup15q Allianc Scientific Meeting in California. During this meeting it was
estimated, with research support, that approximately 1-3% of the Autism
population suffers from a duplication of chromosome 15. Along with seizures,
individuals with this duplication may also suffer from sleep problems and poor
muscle tone, all of which are common features of Autism. The University of
California presented finding from analysis on conducted on postmortem brain
tissue from eight people with 15q duplication, 37 people with idiopathic (no
known genetic link) Autism, and 30 controls. This team from UC found that
specific genes stood out, with altered expression, in those with Autism,
compared to controls. What they found is that those with idiopathic autism, or
the individuals who have Autism with no known genetic link, show the same
genetic patterns as those with the 15q duplication. They found that these
groups of altered genes may be related to the structure and function of the
junctions between neurons, known as synapses, and may also be related to the
function of immune cells in the brain.
Believe me that is a lot to understand,
but it all looks very promising. Deletions of 15q also have major health impacts,
which mirror some symptoms of Autism. Deletions from the maternal contribution
of 15q produce Angelman Syndrome, a severe mental
retardation and deletion from the paternal contribution produce Prader-Willi Syndrome, a
life threatening developmental delay disorder. It sounds like researchers are
starting to unlock the link between genetic testing and Autism. I hope through
these many research studies and testing they can produce genetic therapy to
alleviate the effects Autism has on those who suffer from it.
For more about Idic(15), please refer to
this very informative paper.
To read more about Autism and Chromosome
15, please refer to this blog by Autism
Speaks.
To read more about Chromosome 15, please
refer to this article.
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