Archives for category: Genetics

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.

Read more at…

SFARI, May 2012.

Children with autism carry twice as many new and damaging genetic mutations as typically developing children, according to a large study published today in Neuron.

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.

Read more at…

SFARI, April 2012.

Several hundred genes are likely involved in autism, according to the latest trio of studies looking at the genomes of children with the disorder. But let’s not forget that one of the most intriguing genetic links has been known for decades. Autism affects four times as many boys as girls. And at the level of DNA, there’s only one difference between the sexes: Girls have two X chromosomes, boys an X and Y.

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.

Read more at…

SFARI, April 2012.

In spring 2007, half-a-dozen scientists huddled around a laptop at a pub in Cambridge in the United Kingdom, to see the preliminary results from the largest ever genetic study of multiple sclerosis (MS). Expectations were high. Three decades had passed since the last genes were discovered to have a link to MS, in a large genomic region called the major histocompatibility complex (MHC).

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 report included data from almost 4,000 people with MS. In August 2011, the consortium published an even bigger association study. After screening the genomes of nearly 10,000 people with MS, the group found dozens of genetic variants significantly associated with the disease. An intriguing proportion of these variants fall near genes related to the immune system, bolstering the notion that MS is fundamentally an auto-immune disease that leads to brain degeneration, rather than the other way round. “This disease has an astonishingly immunological flavour,” says Alastair Compston, head of clinical neurosciences at the University of Cambridge and another founding member of the IMSGC.

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

Read more at…

Nature, April 2012.

It’s been almost a year since I wrote about my genetic testing results from 23andMe. That’s because, despite paying $5 a month for the site’s mandatory Personal Genome Service®, I rarely look at it.

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.

Read more at…

The Last Word on Nothing, March 2012.

In a mouse model of Alzheimer’s disease, memory problems stem from an overactive enzyme that shuts off genes related to neuron communication, a new study says.

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.”

Read more at…

HHMI News, February 2012.

For most animals, the number of males in a population is about the same as the number of females. And that makes sense, evolutionarily. If a population were skewed toward females, for instance, males would become a hot commodity and each one would have a better chance of mating than would a male in a balanced population. Eventually, parents who had boys would accumulate more grandchildren, and the genes for producing boys would spread until the sex ratio evened out.

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.

Read more at…

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.

Nature, for all of its free-wheeling weeds and lightning strikes, is also full of biological regularity: the rows of an alligator’s teeth, the stripes on a zebrafish, the spacing of a chicken’s feathers. How do these patterns arise?

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.)

Read more at…

Smithsonian’s Surprising Science, February 2012.