Researchers can create sets of mutated DNA sequences quickly, cheaply
Some 10 million points of genetic variation are scattered across a molecule of DNA, and those variations make us who we are as individuals. But in some cases, those variants contribute to diseases, and it's a major challenge for scientists to distinguish between harmless variants and those that are potentially hazardous to our health.
Now, researchers at Washington University School of Medicine in St. Louis have developed a new technique to cheaply and rapidly create myriad sets of DNA fragments that detail all possible genetic variants in a particular stretch of DNA. By studying such DNA fragments, scientists can more easily distinguish between genetic variants linked to disease and those that are innocuous.
The findings, published Oct. 3 in Nature Methods, allow researchers to create sets of DNA variants in a single day for a few hundred dollars. Current methods take up to a week and cost tens of thousands of dollars.
"As a pediatric neurologist who does a lot of genetic studies of kids with developmental disabilities, I frequently will scan a patient's whole genome for genetic variants," said Christina Gurnett, MD, PhD, the study's senior author and an associate professor of neurology and of pediatrics. "Sometimes I'll find a known variant that causes a particular disease, but more often than not I find genetic variants that no one's ever seen before, and those results are very hard to interpret."
In the past, scientists tested the effect of genetic variants one by one, a laborious process. At a single point in the DNA sequence, they replaced the correct DNA letter - an A, T, C or G - with one of the other three options. Then, they translated that DNA sequence into a protein and evaluated whether the mutated protein behaved differently than the original one.
More recently, researchers have begun creating sets of hundreds of variants in which each letter in a particular DNA sequence is changed, and then testing the set all at once. Such studies have been limited, however, by the high cost of creating those sets.
Postdoctoral researcher Gabriel Haller, PhD, who was working in Gurnett's lab, realized that he could harness common laboratory techniques and tools to create sets of DNA variants without the expensive equipment and reagents that drove up the price.
Haller copied a DNA sequence using the four standard DNA letters and a nonstandard letter known as inosine. Each copy of the sequence was identical except for one inosine, which was located at a random spot and served as a placeholder. Then, he replaced the inosine with one of the standard DNA letters, creating a single mutation in each copy of the sequence.
Gurnett and colleagues are applying this technique to genes associated with aortic aneurysms, a weakening and ballooning of the aortic wall that can be fatal. Over the long term, Gurnett envisions the creation of a catalog listing the effects of every possible variant. The speed and cheapness of the new technique make such a catalog possible.
"Then, when clinicians find a variant that's never been seen before in one of these genes associated with aortic aneurysm, they can go through this catalog and say, 'Yes, this mutation does have a negative effect on that protein, so it's likely harmful'," Gurnett said. "It would help them decide what to tell the patient. This would be one piece of the big interpretation puzzle for genetic mutations."
Judy Martin Finch | EurekAlert!
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
14.12.2018 | Power and Electrical Engineering
14.12.2018 | Physics and Astronomy
14.12.2018 | Physics and Astronomy