Chromosomal Abnormalities Play Subs. Role in Autism

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Copied from Schaefer Autism Report:

Chromosomal Abnormalities

Play Substantial Role In Autism

ScienceDaily - Genome-wide scans of families affected by autism spectrum

disorder (ASD) have revealed new evidence that previously unknown chromosomal

abnormalities have a substantial role in the prevalent developmental disorder,

according to a new report. Structural variants in the chromosomes were found to

influence ASD with sufficiently high frequency to suggest that genomic analyses

be considered in routine clinical workup, according to the researchers.

" Historical studies in identical twins and their families have provided

strong evidence for a genetic basis of autism, " said Scherer of The

Hospital for Sick Children and the University of Toronto. " Last year, with the

Autism Genome Project Consortium, we did an initial study to look at the rate of

chromosomal changes in autism. Now, we've really pinned down those numbers. "

Autism is a complex developmental disorder found in about one in every 165

children, making it one of the most common forms of developmental disability of

childhood. Individuals with ASD have deficits in social interaction and

communication and show a preference for repetitive, stereotyped activities.

Structural changes, including gains and losses of genes as well as chromosomal

translocations (in which a chromosomal segment ends up in the wrong place) or

inversions (in which a portion of the genome is oriented backwards) have been

previously identified in some individuals with ASD, but their causal role hasn't

been clear.

In the new study, the researchers examined structural abnormalities in 427

unrelated ASD cases using both microarray analysis and karyotyping. Microarrays

can detect " unbalanced " genetic changes that alter the number of copies of a

particular gene. Karyotyping, in which chromosomes are viewed under the

microscope, can identify " balanced " translocations or inversions that might

otherwise be missed by microarrays.

While most chromosomal abnormalities were inherited, the researchers found

that seven percent of children with autism carry structural changes in the

genome that are not found in their parents. The rate of such de novo changes in

the general population is typically less than one percent, Scherer said.

The researchers detected 13 regions of the genome with overlapping or

recurrent chromosomal changes in unrelated people with autism, suggesting that

genes located at these sites may cause or add to the complexity of the

condition. The most prevalent change, occurring in one percent of ASD cases, was

found on chromosome 16, they reported. The altered portion of chromosome 16 has

structural characteristics that make it more prone to errors, Scherer noted.

In a subset of ASD cases, the researchers found abnormalities in several

genes known to be involved in neuron function. They also identified at least two

sites that have previously been linked to mental retardation.

" Our understanding of the full etiologic role of structural variation in

ASD will require genomic and phenotypic analyses of more cases (and their

families) and population controls, " the researchers concluded. As a first step

toward achieving the desired numbers, the researchers have established a new

Autism Chromosome Rearrangement Database, which allows integration of their new

data and all other molecular information with the wealth of karyotypic data

gathered over the years.

In light of the new findings, Scherer's team also calls for new testing in

the clinic.

" From our current data it is already apparent that for a proportion of

individuals, it will be possible to describe their ASD based on the underlying

structural characteristics of their genome, " they wrote.

" If we found certain changes, we could then watch those children closer, "

Scherer added, noting the critical importance of early diagnosis for autism.

This research was published online Jan. 17th in the American Journal of

Human Genetics, a publication of Cell Press.