The technique could lead to affordable personalized medicine, potentially revealing predispositions for afflictions such as cancer, diabetes or addiction.
"There is a clear path to a workable, easily produced sequencing platform," said Jens Gundlach, a University of Washington physics professor who leads the research team. "We augmented a protein nanopore we developed for this purpose with a molecular motor that moves a DNA strand through the pore a nucleotide at a time."
The researchers previously reported creating the nanopore by genetically engineering a protein pore from a mycobacterium. The nanopore, from Mycobacterium smegmatis porin A, has an opening 1 billionth of a meter in size, just large enough for a single DNA strand to pass through.
To make it work as a reader, the nanopore was placed in a membrane surrounded by potassium-chloride solution, with a small voltage applied to create an ion current flowing through the nanopore. The electrical signature changes depending on the type of nucleotide traveling through the nanopore. Each type of DNA nucleotide – cytosine, guanine, adenine and thymine – produces a distinctive signature.
The researchers attached a molecular motor, taken from an enzyme associated with replication of a virus, to pull the DNA strand through the nanopore reader. The motor was first used in a similar effort by researchers at the University of California, Santa Cruz, but they used a different pore that could not distinguish the different nucleotide types.
Gundlach is the corresponding author of a paper published online March 25 by Nature Biotechnology that reports a successful demonstration of the new technique using six different strands of DNA. The results corresponded to the already known DNA sequence of the strands, which had readable regions 42 to 53 nucleotides long.
"The motor pulls the strand through the pore at a manageable speed of tens of milliseconds per nucleotide, which is slow enough to be able to read the current signal," Gundlach said.
Gundlach said the nanopore technique also can be used to identify how DNA is modified in a given individual. Such modifications, referred to as epigenetic DNA modifications, take place as chemical reactions within cells and are underlying causes of various conditions.
"Epigenetic modifications are rather important for things like cancer," he said. Being able to provide DNA sequencing that can identify epigenetic changes "is one of the charms of the nanopore sequencing method."
Coauthors of the Nature Biotechnology paper are Elizabeth Manrao, Ian Derrington, Andrew Laszlo, Kyle Langford, Matthew Hopper and Nathaniel Gillgren of the UW, and Mikhail Pavlenok and Michael Niederweis of the University of Alabama at Birmingham.
The work was funded by the National Human Genome Research Institute in a program designed to find a way to conduct individual DNA sequencing for less than $1,000. When that program began, Gundlach said, the cost of such sequencing was likely in the hundreds of thousands of dollars, but "with techniques like this it might get down to a 10-dollar or 15-minute genome project. It's moving fast."
For more information, contact Gundlach at 206-616-2960, or email@example.com
Vince Stricherz | EurekAlert!
Researchers find new mutation in the leptin gene
24.06.2019 | Texas Biomedical Research Institute
Straight to the heart
24.06.2019 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft
From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.
Reducing machine downtime, manufacturing defects, and excessive scrap
The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.
Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...
The well-known representation of chemical elements is just one example of how objects can be arranged and classified
The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...
Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.
Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...
Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.
The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...
24.06.2019 | Event News
29.04.2019 | Event News
17.04.2019 | Event News
24.06.2019 | Event News
24.06.2019 | Agricultural and Forestry Science
24.06.2019 | Life Sciences