MIT Technology Review looks at a process for sequencing DNA that could bring the cost down to $100 for a whole genome within 5 years (by 2012) and work on long sequences of DNA. The new method will also allow reading of long sequences of DNA. Small structural changes in DNA, such as deletions or inversions of short sequences, play a significant role in human variability which are tough to find with short DNA reads. Longer reads will also allow scientists to look at collections of genetic variations that have been inherited together, known as haplotypes. Recent research suggests that in some cases, maternal or paternal inheritance can impact the severity of the disease. The project funding runs to Oct 31, 2012.
Complete Genomics aims to speed the process by detecting entire “words,” each composed of five DNA letters. Drmanac likens the technology to Google searches, which query a database of text with keywords. Further speeding up the process with novel chemistry and advances in nanofabrication, the companies will develop a device that can simultaneously read the sequence of multiple genomes on a single chip.
To accomplish the new sequencing, scientists first generate all possible combinations of five-letter DNA segments, given the four letters, or bases, that make up all DNA. These segments are labeled with different types of fluorescent markers and added in groups to a single-stranded molecule of DNA. When a particular segment matches a sequence on the strand of DNA to be read, it binds to that part of the molecule. A specialized camera then snaps a picture–the different fluorescent signals indicate the sequence at specific points along the strand of DNA. The process is repeated with different five-letter DNA combinations, until the entire molecule is sequenced. The approach is feasible because of the recent availability of cheap DNA synthesis, making it much more efficient to generate libraries of these DNA segments.
Each DNA molecule will be threaded into a nanofluidics device, made by Philadelphia-based BioNanomatrix, lined with rows of tiny channels. The narrow width of the channels–about 100 nanometers–forces the normally tangled DNA to unwind, lining up like a train in a long tunnel and giving researchers a clear view of the molecule
The big difference from any other approach is that they are looking at physical location at the same time they are looking at sequence information. Sequencing methods currently in use sequence small fragments of DNA and then piece together the location of each fragment computationally, which is more time consuming and requires repetitive sequencing.
BioNanomatrix has already shown that long pieces of DNA–two million letters in length–can be threaded into the channels of existing chips. But now researchers need to develop chips with many more channels, so that multiple genomes’ worth of DNA can be sequenced simultaneously.
The main hurdle for Complete Genomics will be to generate fluorescent labels that can be easily and accurately detected.
News about Bionanomatrix.
U.S. National Institute of Standards and Technology Advanced Technology Program (NIST-ATP) funding of $8.8 million to develop a system capable of sequencing the entire human genome in eight hours at a cost of less than $100.