New rapid technique to map DNA by melting base pairs
26 July 2010
A new method for rapidly mapping the base pairs of a DNA
molecule has been developed by researchers in Sweden and Denmark. The
technique could be used to find out more easily whether someone is
carrying a genetic predisposition to certain diseases.
The aim is that the new technique could be used to diagnose and
characterise diseases that are caused by significant changes and
mutations in the genetic make-up, known as structural variations,
that are associated with, for example, cancer, autism and several
In addition, the method could be of use in criminal
investigations, because it might speed up identification of
The results are published in the latest issue of the journal
Proceedings of the National Academy of Sciences of the USA (PNAS).
The technique, which has recently been patented, uses the fact
that different parts of the DNA molecule melt at different
temperatures. A central component of the DNA molecule is the
nucleobase pairs. These are found in two pair varieties: AT, which
stands for adenine and thymine; and GC, which stands for guanine and
cytosine. The GC pair is more firmly bound and requires a higher
temperature to melt.
By first stretching out the tightly twisted DNA molecule in a
nanochannel and then heating it up so that only the AT pair melt, it
is possible to obtain a ‘barcode' of the person's 46 chromosomes. In
order to make certain parts darker than others, the DNA molecule
must be stained. The parts that melt — the AT parts — emit less
fluorescence and become dark fields in the barcode.
The image produced shows the rough composition of the DNA
molecule, and thus that of the chromosome. Such barcodes are nothing
new, but this approach to creating the barcodes is completely new.
With this method, the DNA analysis process becomes significantly
shorter, from 24 hours to around one or two hours.
"The technique is quicker, easier and cheaper than existing
methods. Therefore we hope that it can be used in hospitals in the
future. Mapping a person's genome, or genetic make-up, is currently
an expensive and complicated process", said Jonas Tegenfeldt,
researcher in Solid State Physics at Lund University and one of the
senior authors of the article.
"The barcode technique could be a simple way to identify what
types of virus and bacteria we are dealing with. We can also find
out whether something has gone wrong in the human genome, because it
is possible to see if any part of the chromosome has moved for any
reason. This is what happens in certain diseases", explains Jonas
Tegenfeldt, adding that beyond all the applications an important
motivation for the research is still ‘just' basic scientific
A further advantage of this barcode technique over other
techniques is that only one DNA molecule is required. The fact that
the DNA does not have to be amplified also means that it is easy to
compare a number of cells and thereby discover any differences
The method provides a rough image of the genome, but compared to
other similar methods, such as chromosome banding, the image is
still a thousand times sharper. The fact that the measurements must
be performed on each molecule individually could also pose a
limitation; it is not easy to obtain an average from a large number
1. Walter Reisner, Niels B. Larsen, Asli Silahtaroglu, Anders
Kristensen, Niels Tommerup, Jonas O. Tegenfeldt, and Henrik
Flyvbjerg. Single-molecule denaturation mapping of DNA in
nanofluidic channels, Proceedings of the National Academy
of Sciences of the USA (PNAS). Published online before print
July 7, 2010.