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ots-News: English

Speeding up genetic diagnosis of Huntington's disease

10.01.2019 | 11:00 Uhr | Ressort: Economy | Quelle: Presseportal

Bern (ots) - Elongated segments of DNA cause Huntington's disease
and certain other disorders of the brain. Researchers funded by the
SNSF have developed a method to determine the length of the mutated
genes quickly and easily.

People with Huntington's disease suffer from jerky body movements
and decreasing mental abilities. The condition usually leads to death
15-20 years after diagnosis. The cause of the disease is a region in
the Huntingtin gene that is longer than in healthy people. The
mutation causes the destruction of brain cells.

Five-minute measurement

Determining the length of this gene involves tedious laboratory
work and currently takes more than five hours. The team of Vincent
Dion, holder of an SNSF professorship at the University of Lausanne,
together with collaborators from Toulouse, have developed a reliable
method for measuring the length of the responsible DNA region which
produces a result within only five minutes (*). The whole diagnosis
is thus speeded up more than three times.

For the analysis, the team extracts the DNA from blood cells,
amplifies the concerned region and determines its size with a newly
developed chip. The chip holds two small, funnel-shaped chambers a
fraction of a millimetre wide. Voltage and pressure are applied to
these chambers so as to separate the electrically charged DNA
fragments according to their size. The smaller fragments are pushed
down the funnel much more than the large ones. By adding a
fluorescent dye, the researchers can easily detect the exact position
of the fragments under a microscope and deduce their length.

The variable length of the DNA fragments is caused by a repetition
of three nucleotides of the genetic code (CAG) - typical for
trinucleotide diseases like Huntington's. The mutation leads to
destructive changes in the encoded protein that are currently not
fully understood, but the protein produced by the mutated gene is
known to be toxic to brain cells. Healthy people have 35 or less of
these repeats, whereas most patients have 40 or more. Knowing the
exact size is important for forecasting and managing the incurable
disease. "Our method is more sensitive and faster than the current
methods", says Vincent Dion.

The project was a collaboration with the group of Aurélien Bancaud
from the Laboratoire d'analyse et d'architecture des systèmes in
Toulouse, who developed and patented the device. It is licensed out
to the company Picometrics Technologies, which has developed the
device under the name µLAS.

Cutting out the bad repeats

Huntington's disease is only one of over twenty known
trinucleotide diseases. Others are spinocerebellar ataxia, fragile X
syndrome, myotonic dystrophy and Friedreich's ataxia. Currently there
is no treatment available for these hereditary diseases. A certain
amount of hope is provided by Vincent Dion, who recently developed a
method for shortening the fragments with a CRISPR-Cas-based approach
(**). "It is, however, still a long way from this proof of concept in
cell cultures to a potential medical application", says Vincent Dion.

(*) R. Malbec et al: µLAS: Sizing of expanded trinucleotide
repeats with femtomolar sensitivity in less than 5 minutes.
Scientific Reports (2018). DOI: 10.1038/s41598-018-36632-5

(**) C. Cinesi et al.: Contracting CAG/CTG repeats using the
CRISPR-Cas9 nickase. Nature Communications (2016). DOI:
10.1038/ncomms13272 http://dx.doi.org/10.1038/ncomms13272


Promoting young researchers

SNSF Eccellenza Grants allow tenure-track assistant professors to
select a new research team and lead an ambitious scientific project.
SNSF Eccellenza Professorial Fellowships cover the salaries of
assistant professors as well as their project costs. The new scheme
replaces the SNSF professorship grant, which has supported 691
researchers since its launch in 2000 - with great success: around 80%
of grantees went on to obtain a professorship at a higher education
institution in Switzerland or abroad.

Eccellenza: http://www.snf.ch/en/funding/careers/eccellenza


The text of this press release, a download image and further
information are available on the website of the Swiss National
Science Foundation: http://www.snf.ch/en/researchinFocus/newsroom/Pag

Professor Vincent Dion
Center for Integrative Genomics
University of Lausanne
Tel.: +44 75 54 39 44 09
E-mail: vincent.dion@unil.ch