To confirm that result, the researchers screened DNA from an additional 532 subjects with autism. They found two additional subjects with the same deletion (0.4%), which was seen in none of the 465 controls. Combining the two samples produced a total prevalence of 16p11.2 deletions of 0.6 percent.
The 16p11.2 region is flanked on both sides by bands of segmental duplications, short strings of nearly identical DNA that predispose to the loss, shuffling or amplification of this region during 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.
The most common known genetic cause of autism, linked to about one to three percent of cases, 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 (www.idic15.org). The chromosome 16 deletion, by contrast, is not consistently associated with intellectual disability.
"Although this only explains about one-half of one percent of autism," said co-author William Dobyns, professor of human genetics and pediatrics at the University of Chicago, "it provides the best clues yet for finding the specific genetic changes that lead to the disease. This is a small region with a limited number of genes, including several strong candidates, each of which merits a closer look. The next step is to find the specific gene or genes involved. There may be one gene within that deletion that is at the core of the problem."
|Contact: John Easton|
University of Chicago Medical Center