Recurrent genetic “microdeletion linked to autism

January 9th, 2008 - 4:58 pm ICT by admin  

Washington , Jan 9 (ANI): Researchers from the University of Chicago Medical Center, the University of Illinois at Chicago , and the Roswell Park Cancer Institute have discovered that the deletion of a tiny part of chromosome 16, callled 16p11.2, is linked to autism.

The study was led by Susan Christian, PhD, associate professor of human genetics at the University of Chicago .

This genetic microdeletion, despite of being detected in only four out of 712 subjects with autism (0.6pct), is the second most common recurrent genomic disorder associated with autism, affecting almost 1 out of 160 children in the United States.

“We suspect that 16p11.2 microdeletions are a risk factor for autism spectrum disorders generally and may cause mild autism in some families. By disturbing the network of affected genes, this loss of selected genes may underlie the development of autism,” said Dr. Christian.

This deletion results in the loss of about 25 known genes.

“Twelve of those genes appear to be part of a single genetic network that includes genes involved in cell-to-cell signaling and interaction. At least three of the deleted genes are primarily expressed in the brain and are thought to influence behavior which makes them very promising candidates for autism, said first author Ravinesh A. Kumar, PhD. postdoctoral scientist in human genetics at the University of Chicago .

It was also suspected that the lost or damaged genes may be involved in other cognitive, language and social impairments.

In order to find genes associated with autism, the entire genomes of 180 subjects with autism was scanned to search for submicroscopic pieces of DNA that were either lost or mistakenly duplicated in patients diagnosed with autism.

It was first found that 2 out of those 180 (1.1pct) had a deletion in region 16p11.2, on the short arm of chromosome 16. Besides, none of the 372 control subjects was found to have the same deletion.

For confirmation of this result, DNA from an additional 532 subjects with autism was scanned. They found two additional subjects with the same deletion (0.4pct), not seen in any of the 465 controls. When the two samples were combined, a total prevalence of 16p11.2 deletions of 0.6 percent was produced.

The 16p11.2 region is lined on both sides by bands of segmental duplications, short strings of nearly identical DNA that affect the loss, shuffling or amplification of this region at the time of genetic recombination.

“Many human diseases are caused by these types of chromosomal rearrangements, however, this is the first recurrent microdeletion in autism too small to be seen under a microscope,” said Christian.

However, the most common known genetic cause of autism is a much larger duplication of part of chromosome 15, involving about a dozen genes. The chromosome 15 abnormality is associated with autism as well as intellectual disability. On the other hand, the chromosome 16 deletion is not consistently associated with intellectual disability.

The study was recently published online by the journal Human Molecular Genetics. (ANI)

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