Archives for the month of: March, 2010

This June marks 10 years since two independent teams of geneticists unveiled the first draft of the human genome.

After years of bitter rivalry, Francis Collins, then the director of the US National Human Genome Research Institute and Craig Venter together made the announcement from the East Room of the White House.

Then-president Bill Clinton predicted that the feat, which cost billions of dollars and took more than a decade, would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”

We’re clearly not there yet. So what exactly have we gained from knowing the sequence of 3 billion base pairs?

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SFARI, March 2010.

Young mouse models of fragile X syndrome show a significant lag in the development of synapses, the connections between neurons, according to a study published in February in Neuron.

The researchers spotted the delay in the barrel cortex, the region of the mouse sensory cortex that responds to whisker sensation. Their findings suggest that a similar mistiming may be responsible for the sensory problems — such as hypersensitivity to touch and sound — sometimes seen in people with fragile X syndrome.

The study marks the first time that researchers have identified a functional synaptic problem in the development of fragile X syndrome, a genetic disease characterized by mental retardation and, often, autism.

“It basically awakens the field to the fact that we need to focus on earlier time points in development,” says Ricardo Galvez, assistant professor of psychology at the University of Illinois at Urbana-Champaign, who was not involved with the work. “Now we can start looking at how drugs affect abnormalities in these earlier time points, with the hope that we can somehow turn back the clock.”

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SFARI, March 2010.

There are several short periods during development in which our brains are ‘plastic’ — meaning that neuronal connections appear and disappear depending on how much they are used.

The brain can only adapt to new experiences during these windows of plasticity. But researchers may have found a way to reopen the windows, according to a paper published late last month in Science.

The visual system is the best platform to study plasticity. For example, if you shut one eye of a mouse during a ‘critical period’ of development, around the 28th day of its life, its brain will rewire so that it only processes light from the other eye. In the 1970s, scientists Tortsen Wiesel and David Hubel were the first to demonstrate this phenomenon in a one-week-old kitten. This critical period also exists in people.

A decade ago, scientists discovered that plasticity can be induced or delayed by drugs that mimic inhibitory interneurons — cells that dampen nerve impulses.

In the new study, the researchers transplanted fetal interneurons into the brains of young mice and shut one of the animals’ eyes during the normal critical period. After the window closed, the researchers opened the eye and, as expected, the mouse could not see from it.

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SFARI, March 2010.

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Over the past couple of years, study after study has found specific DNA deletions and duplications, called copy number variations (CNVs), that independently increase an individual’s risk of autism.

But what if you carry more than one CNV?

A study published online 14 February in Nature Genetics is among the first to focus on the combined risk of having multiple CNVs for psychiatric disease.

Screening more than 20,000 children with intellectual disability,Evan Eichler and an international group of colleagues found a deletion on chromosomal region 16p12.1 in 42 individuals, or about 0.2 percent — about four times the frequency they saw in the healthy control population.

In addition to developmental delay, children who carry the 16p12.1 deletion may also have congenital heart defects, seizures and severe growth abnormalities, the researchers found. The deletion joins three others on the short arm of chromosome 16 that are associated with autism or other neurodevelopmental disorders.

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SFARI, March 2010.

Brian Dugan, dressed in an orange jumpsuit and shackles, shuffled to the door of Northwestern Memorial Hospital in downtown Chicago, accompanied by four sheriff deputies. It was the first time that Dugan, 52, had been anywhere near a city in 20 years. Serving two life sentences for a pair of murders he had committed in the 1980s, he was now facing the prospect of the death penalty for an earlier killing.

Dugan was here on a Saturday this past September to meet one of the few people who might help him to avoid that fate: Kent Kiehl, a neuroscientist at the University of New Mexico in Albuquerque. Dugan, Kiehl and the rest of the entourage walked the length of the hospital, crossed a walkway to another building, and took the lift down to a basement-level facility where researchers would scan Dugan’s brain using functional magnetic resonance imaging (fMRI). Todd Parrish, the imaging centre’s director, offered plastic zip ties to replace the shackles — no metal is allowed in the same room as the scanner’s powerful magnet — but the guards said they weren’t necessary. Dugan entered the machine without restraints, and Parrish locked the door — as much to keep the guards and their weapons out as to keep Dugan in.

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Nature, March 2010.

Or, listen to the podcast.

A new technique can simultaneously sequence DNA and pinpoint some of the chemical modifications that turn genes on or off, according to a report published 9 May in Nature Methods.

In particular, the technique reveals methyl groups bound to DNA bases. DNA methylation — one of several types of ‘epigenetic’ changes — allows organisms to express genes at various times, and in different tissues, without changing the underlying DNA code.

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SFARI, May 2010.

 

Honoring a pioneer of geriatric medicine, the late Michael Freedman, MD, professor emeritus of medicine, an Alzheimer’s Disease Lecture was held on January 15. Dr. Freedman, founder of the Department of Medicine’s Division of Geriatrics, died in February. He was the author of nearly 200 scientific papers investigating the biology of aging, dementia, and Alzheimer’s disease. His wife, Cora, and children, Lawrence and Deborah, joined faculty members and other distinguished guests in Farkas Auditorium to hear the presentation, given by Lisa Mosconi, PhD, research assistant professor of psychiatry.

Dr. Mosconi discussed several of her ongoing studies on the use of positron emission tomography (PET)—a safe and painless brain-imaging technique—to better understand the cause and course of Alzheimer’s. A progressive and fatal brain disease causing severe memory loss, Alzheimer’s affects 5.3 million Americans. The early-onset form, affecting 1 to 2% of all cases, stems from mutations in three specific genes. It’s the more common late-onset variety, in which symptoms appear after age 65, that intrigues Dr. Mosconi. For many years, this type was associated mostly with aging and environmental influences such as diet and education, but the researchers have identified a familial component to late-onset Alzheimer’s.

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NYU News & Views, March/April 2010.

In the U.S., moving a drug from the lab bench to the pharmacy’s shelves takes about 10 years. That’s because the Food and Drug Administration (FDA) sets a high bar — the rigorous three-stage clinical trial system — to ensure that drugs are safe and effective.

Late last month, the agency announced that it’s pushing a controversial autism treatment through the system a bit more quickly.

CM-AT, a drug made by New York biotech CureMark, is a powder that helps children with autism digest proteins and, supposedly, improves brain function. Its creators haven’t published any information yet about the drug’s effectiveness or how it works. But last year, after submitting positive preliminary results to the FDA, the company began a stage-III clinical trial at 12 medical centers.

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SFARI, March 2010.