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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SFARI, May 2012.

Michael Wigler, professor at Cold Spring Harbor Laboratory in New York, and his collaborators sequenced the exome, or protein-coding parts of the genome, using DNA isolated from blood cells from 343 children with autism and their family members. The findings lend statistical heft to three other exome-sequencing studies published inNature earlier this month.

“This fourth Musketeer is the largest of all four, and really puts the nail in the coffin” regarding the abundance of damaging mutations in autism, says Jonathan Sebat, associate professor of psychiatry and cellular and molecular medicine at the University of California, San Diego, who was a postdoctoral fellow in Wigler’s laboratory but was not involved in the new work.

The new study, as well as two of the older papers, tapped into the Simons Simplex Collection (SSC), a genetic and medical repository of some 2,700 families with only one child with autism and unaffected siblings and parents.

Unlike the other three papers, the new one also identified intriguing genetic links between autism and fragile X syndrome, the most common inherited form of intellectual disability. An estimated one-third of children with fragile X are also diagnosed with autism.

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SFARI, April 2012.

So why don’t we hear more about that Y?

The male chromosome only carries about 60 genes, of which 2 have been linked to autism. Nevertheless, some new research on children born with extra sex chromosomes suggests that there may be more than meets the Y.

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SFARI, April 2012.

Using the pub’s wireless Internet connection, one of the researchers eagerly downloaded the first batch of data. It was disappointing: the analysis found no gene variants outside the MHC that were associated with MS. “We thought, all this work and once again MS eludes us,” recalls David Hafler, one of the leaders of the International Multiple Sclerosis Genetics Consortium (IMSGC).

The next morning, when the researchers convened again at the University of Cambridge, they were in for a pleasant surprise. “The guy who had downloaded the data said: ‘Oh, I made a mistake’,” recalls Hafler, who is now head of neurology at Yale University. When the analysis was done again, the program identified variants near two genes that play an important role in the workings of immune cells.

The hope, Compston says, is that studying these variants will point researchers towards shared biological pathways that would make good targets for drugs.

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Nature, April 2012.

It’s not that I’m scared of the data (been there), and not because I forgot — every six or eight weeks I get an email from the company saying things like, You have 8 new results from 23andMe! New discoveries have been made about your DNA! I hadn’t visited the site because, frankly, I was bored of it. How many times is one expected to look sort-of-interesting, sort-of-meaningless risk calculations and ponder healthier ways to live?

Then at a conference last week, while trying to make small talk with a scientist, I mentioned my 23andMe subscription. Turns out he has one, too. “Isn’t it funny when you get those messages from your distant relatives?” he said. I told him I didn’t know what he meant. “I get them all the time,” he said, shaking his head.

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The Last Word on Nothing, March 2012.

When researchers genetically blocked the enzyme, called HDAC2, they ‘reawakened’ some of the neurons and restored the animals’ cognitive function. The results, published February 29, 2012, in the journal Nature, suggest that drugs that inhibit this particular enzyme would make good treatments for some of the most devastating effects of the incurable neurodegenerative disease.

“It’s going to be very important to develop selective chemical inhibitors against HDAC2,” says Howard Hughes Medical Institute investigator Li-Huei Tsai, whose team at the Massachusetts Institute of Technology performed the experiments. “If we could delay the cognitive decline by a certain period of time, even six months or a year, that would be very significant.”

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HHMI News, February 2012.

But that explanation, known as Fisher’s Principle, is too pat. There are many species that, for a variety of environmental and social reasons, wind up with an imbalance of males and females. Typically, researchers have said that the female—usually the one that invests more time and energy into her offspring—is responsible for skewing the ratio depending on her needs. But a new study in pygmy hippos, published today in Nature Communications, shows that males can influence sex ratios, too.

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Smithsonian’s Surprising Science, February 2012.

The new study, certainly not the last word on DNA, was published last week in The EMBO Journal. The music is Chopin’s Minute Waltz, the subject of another post.

First published on…

The Last Word on Nothing, February 2012.

Sixty years ago, with nothing but numbers, logic and some basic biological know-how, mathematician Alan Turing (best known for his pioneering work on artificial intelligence) came up with an explanation. He proposed that two chemicals—an “activator” and an “inhibitor”—work together, something like a pencil and eraser. The activator’s expression would do something—say, make a stripe—and the inhibitor would shut off the activator. This repeats, and voilà, stripe after stripe after stripe.

On Sunday, researchers reported the first experimental evidence that Turing’s theory is correct, by studying the eight evenly spaced ridges that form on the roof of a mouse’s mouth. (People, by the way, have four such ridges on each side, which help us feel and taste food.)

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Smithsonian’s Surprising Science, February 2012.

Functional mutations in SHANK2 crop up about twice as often in individuals with autism as in typical controls, according to a study published 9 February in PLoS Genetics.

The SHANK2 protein buttresses the synapse, or junction between neurons. The new findings add to already robust evidence from genetic studies and animal models that synaptic proteins — notably SHANK3, neurexins and neuroligins — are important in autism, the researchers say.

But a more surprising finding helps to explain why not everyone who has a SHANK2 mutation has autism. The three individuals with autism known to carry SHANK2 deletions also carry rare deletions or duplications — so-called copy number variations, or CNVs — in an autism-linked segment of chromosome 15. This supports the idea that autism arises not from a single genetic glitch, but from multiple hits to the genome.

“I think many people are still thinking about the genome like the old black-and-white movies from the 1950s: The good guy was in white, the bad guy was in black, and everybody knew what was going on,” says lead investigator Thomas Bourgeron, professor of genetics at the University of Paris Diderot.

But studies like this show that a ‘bad’ genetic glitch isn’t necessarily the only bad guy.

“When we find a single mutation in a patient with autism, we can’t say that we’re done,” Bourgeron says. “We still have to work on the whole genome of these patients to understand exactly what’s going on.”

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SFARI, February 2012.