New Autism Research from the Society for Neuroscience Meeting

I just got home from five days of intense reporting on autism research for SFARI.org at the Society for Neuroscience annual meeting in San Diego.

These are all of my conference reports from the meeting:

Online tools sift through storehouses of brain data

Computer program guides molecular scissors on where to snip

First tadpole model of autism surfaces at conference

Brain’s immune cells boost rapid transmission of signals

Hormone reverses autism-like features in mouse model

Neurons made from people with autism show distinct markers

Gut problems in autism may stem from neuronal connections

Jittery limb movements may predict autism subgroups

Brain findings in autism leave researchers scratching heads

Chemical messenger may drive maternal infection’s effects

Slippery SNPs

About a year ago, researchers in Australia published a study with an incredible claim: A new genetic test, screening for 237 common genetic markers, could predict autism with more than 70 percent accuracy.

The study, published in Molecular Psychiatry, was widely reported in the popular press with its claims largely unquestioned. But as SFARI.org reported at the time, some experts were strongly skeptical.

For one thing, larger studies had looked for common variants, known as single nucleotide polymorphisms, or SNPs, that up the risk of autism — and had come up short.

“The data look interesting but really need to be tested independently before I would believe the results were scientifically sound,” geneticist Stephen Scherer, director of the Centre for Applied Genomics at the Hospital for Sick Children in Toronto, told me at the time. “There is much room for error, both in study design and interpretation, and too much at stake here to get this wrong.”

As it turns out, the study was indeed wrong. Last week, Benjamin Neale and his colleagues from Massachusetts General Hospital reported in the same journal that the 237-marker panel does not predict autism risk — not by a long shot.

Read more at… 

SFARI.org, October 2013. 

Small Deletions, Duplications of DNA May Up Autism Risk

Two new studies have found more small deletions and duplications of DNA in individuals with autism than in controls. These variants may also affect the severity of the disorder.

The studies mined the sequences of exomes, the regions of the genome that code for proteins.

Autism is strongly genetic: Twin studies have estimated that some 50 to 90 percent of cases are caused by genetic factors. Yet all of the genetic studies of autism put together have identified less than half of these genes.

The new studies suggest that some of that missing heritability can be explained by small deletions and duplications of DNA — called copy number variations (CNVs).

“Now that there’s exome data on a substantial number of autism families, you can take advantage of the ability to detect CNVs in exons to find stuff that you couldn’t find before,” notes Jonathan Sebat, associate professor of psychiatry at the University of California, San Diego, who was not involved in either study.

Read more at… 

SFARI.org, October 2013. 

The Big Sell

In his State of the Union address in February, President Obama made a nod to an emerging federal science project with an incredibly lofty goal: to understand how the brain works.

Obama’s oblique mention, delivered before the project was announced—“Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s”—spurred a suggestive tweet from the leader of the National Institutes of Health and a barrage of questions and speculations from the scientific community.

Big budgets ($300 million a year for 10 years) and big goals (measuring every spike from every neuron in the brain) were thrown out in the press. As the New York Timesdescribed it a few days after the State of the Union, the project was “seeking to do for the brain what the Human Genome Project did for genetics.”

That goal, however appealing, is not going to happen. It probably never had a chance of happening. And that’s not such a bad thing.

Read more at…

Slate, October 2013. 

 

The Case for Genealogy

I’ve always considered genealogy a strange hobby. Why do people devote so much of their time towards unearthing fairly trivial information about their long-dead ancestors?

While I was reporting Uprooted, I heard a wide range of answers to this question. But the most poignant response came from Fred Moss, the legal advisor for the Federation of Genealogical Societies.

I had called Moss because I was trying to find examples of legal cases—such as paternity or inheritance scuffles—that inadvertently resulted from online genealogical searches.

Moss hadn’t heard of any such cases; as it turns out, he deals with cases that involve fighting for more access to genealogical records—not those involving emotionally potent online searches. Because of heightened security concerns over the past few years, these records have become more difficult to access. That’s a big problem for Moss and other genealogists, and one that they have trouble communicating to legislatures and the greater public. “The genealogical community,” he told me, “does a woefully inadequate job of explaining why we do what we do and how society benefits from these efforts.”

Read more at… 

Medium, October 2013. 

How Having Three Parents Leads to Disease-Free Kids

This summer, government health officials in the United Kingdom made headlines by announcing that they will let scientists create babies with DNA from three different people. The procedure is a type of in vitro fertilization (IVF) that would allow women with mitochondrial diseases to have healthy babies. If approved by British Parliament, the method, known as mitochondrial replacement, would lead to a historic event: the first genetically modified humans who could pass down those genetic tweaks to their children.

Some bioethicists and media commentators have voiced concerns about the technique’s safety because so far it’s only been tested on human cells in the laboratory. More broadly, they fear it’s a step toward designer babies and eugenics.

It’s worth noting that IVF itself, which merges sperm and egg cells in a lab, also set off debate when it debuted 35 years ago. The procedure carries some small medical risks, such as a slightly increased chance of premature and low-weight babies, and creates many embryos that never get used. But let’s not forget its enormous upside: It has allowed millions of couples to have children who couldn’t otherwise. Mitochondrial replacement isn’t any scarier—or any less impressive. Mitochondrial disease affects only about 1 in 5,000 people. The method will be performed at a few select clinics in the U.K. and will be carefully monitored. If it proves to be safe, then thousands of women will have the option to bear healthy biological children without giving them their disease. And if it’s not safe, it will most likely be banned.

Read more at… 

Popular Science, October 2013. 

The End of Family Secrets?

I’ve been tied to the genealogy community ever since I can remember. My dad was always into it — for decades, he collected old documents and photos, and went on fact-finding trips to libraries and cemeteries, all to fill in the holes of his ever-expanding family tree. As I’ve written about before, I’ve had trouble wrapping my head around his obsession. Why spend so much time digging up the past?

But I may be in the minority. Genealogy is a booming business, with an estimated 84 million people worldwide spending serious money on the hobby.

As it turns out, the industry owes a big part of its recent success to a technology that I’m quite invested in: genetic testing. Several dozen companies now sell DNA tests that allow customers to trace their ancestry. This technology can show you, for example, how closely you’re related to Neanderthals, or whether you’re part Native American or an Ashkenazi Jew. But the technology can just as easily unearth private information—infidelities, sperm donations, adoptions—of more recent generations, including previously unknown behaviors of your grandparents, parents, and even spouses. Family secrets have never been so vulnerable. 

Read more at… 

Only Human, September 2013. 

23 and You

Cheryl Whittle tried her best to fall asleep, but her mind kept racing. Tomorrow was going to be the culmination of three years of research and, possibly, a day that would change her life forever. Around four am she popped two Benadryl and managed to drift off. But in just a few hours she had to be up and ready to go.

Cheryl and her husband, Dickie, are retired, and live in eastern Virginia, way out on the end of the Northern Neck peninsula, which juts like an arthritic finger into Chesapeake Bay. It’s a beautiful and isolated spot, where most people tack up “No Trespassing” signs and stay close to home. The Whittles enjoy their life in the country, but Cheryl was eager that day to make the long drive to meet Effie Jane. She showered, threw on a T-shirt, jeans, and sneakers, dotted make-up on her cheeks, and scrunched a dollop of mousse into her thinning brown hair. There’s nothing showy about Cheryl, not even on a day like this. She’s short and shy, with nine grandchildren and no pretensions. She grabbed a shoulder bag, heavy with the day’s supplies, and kissed Dickie on her way out the door.

Her anxiety mounted as she drove her yellow pick-up past sleepy cornfields, old plantations, and cemeteries, up the peninsula and into mainland Virginia. Then she pulled into the tiny parking lot of Panera Bread in Richmond. She didn’t have to wait long before Effie Jane Erhardt found her—that yellow truck was hard to miss. Effie Jane pulled open the truck’s passenger door and announced, “I’m here!”

Cheryl and Effie Jane found each other through Ancestry.com, a popular website for people trying to fill in their family trees. After several email and phone encounters, each woman felt a kinship that neither had experienced before. Both were born in 1951, and grew up about 20 miles from each other in the Richmond area. They both speak with soft Southern drawls, had traumatic childhoods, are devout Christians, and, as children, felt like outsiders in their own families.

Cheryl quickly got down to business, retrieving a small cardboard box from her bag in the back seat. She opened the top, plucked out a fat plastic tube, and handed it to her friend. Effie Jane held the tube under her mouth and spit—and spit, and spit, and spit. She had never realized how much saliva froths and fizzes. She passed the tube back to Cheryl, who snapped on a plastic cap, gently mixed the tube’s contents, and dropped it in a clear plastic bag with an orange BIOHAZARD label. Then the two women went into Panera for lunch.

Read more at…

MATTER, October 2013.

Autism Genes Are Surprisingly Large

Enzymes called topoisomerases are crucial for the expression of extremely long genes in neurons, according to a study published 5 September inNature. More than one-quarter of these genes are known autism candidates, the study found.

In the process of doing these analyses, the researchers stumbled on something surprising about autism genes in general: They’re three to four times longer than the average gene expressed in neurons.

“It’s pretty remarkable that, at least to my knowledge, no one had noticed this before,” notes Benjamin Philpot, associate professor of cell biology and physiology at the University of North Carolina, Chapel Hill, and one of the study’s leaders. “But the genes are definitely much longer. It’s very striking.”

Read more at… 

SFARI.org, September 2013. 

Genome-Editing Tools Compose New Models of Autism

Genome sequencing studies of individuals with autism have left researchers with an embarrassment of riches: hundreds of single-letter mutations of uncertain relevance to the complex brain disorder.

Thanks to a suite of new tools in synthetic biology, it’s now
possible to test the relevance of these genetic glitches quickly and
cheaply by inserting them into living cells in the lab and observing the
effects.

Synthetic biologists manipulate the body’s building blocks — DNA, RNA
and proteins — to engineer structures that do not exist in the natural
world.

On 15 February, two groups published back-to-back papers in Science
describing a new synthetic technology known as CRISPR, for clustered
regularly interspaced short palindromic repeats. This method allows
researchers to create molecular scissors that cut and paste essentially
any mutation into the genome of any cell, including a human stem cell.

In the 9 May issue of Cell, researchers reported that they had used these molecular scissors to insert several mutations into mouse cells at the same time.

“What took us, in the past, three years to make — a triple-knockout mouse — we can do now basically in three weeks,” says Rudolf Jaenisch, lead investigator of the Cell study and professor of biology at the Massachusetts Institute of Technology (MIT) and the Whitehead Institute.

Read more at… 

SFARI.org, September 2013.