By creating genetically engineered fish, two independent groups have identified genes in an autism hotspot on chromosome 16 that influence head size and brain development. One of the studies appears today in Nature.
A 29-gene stretch of chromosome 16 known as 16p11.2, or 16p, is deleted or duplicated in roughly one percent of individuals with autism and duplicated in some individuals with schizophrenia. Researchers have struggled to sort out which genes in the region contribute to features of these disorders.
Using zebrafish allows for an unbiased screen of individual genes, says Nicholas Katsanis, professor of cell biology at Duke University in Durham, North Carolina, and lead investigator of the Nature study. “We tested all of them with exactly same protocol, with no prior expectation of what we were going to find,” he says.
His study shows that suppressing a little-known gene called KCTD13 in zebrafish leads to a 20 percent increase in head size. Conversely, expressing too much of the gene leads to a 20 percent decrease in head size.
This seems to mirror what happens in people. Individuals lacking one copy of 16p often have abnormally large heads, dubbed macrocephaly, whereas those with an extra copy tend to have abnormally small heads, or microcephaly.
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