Nav: Home

Speeding up genetic diagnosis of Huntington's disease

January 10, 2019

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

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.


Project in the SNSF research database P3

The text of this press release, a download image and further information are available on the website of the Swiss National Science Foundation: > Research in Focus > Media > Press releases

Swiss National Science Foundation (SNSF)

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Don't Fear Math
Why do many of us hate, even fear math? Why are we convinced we're bad at it? This hour, TED speakers explore the myths we tell ourselves and how changing our approach can unlock the beauty of math. Guests include budgeting specialist Phylecia Jones, mathematician and educator Dan Finkel, math teacher Eddie Woo, educator Masha Gershman, and radio personality and eternal math nerd Adam Spencer.
Now Playing: Science for the People

#518 With Genetic Knowledge Comes the Need for Counselling
This week we delve into genetic testing - for yourself and your future children. We speak with Jane Tiller, lawyer and genetic counsellor, about genetic tests that are available to the public, and what to do with the results of these tests. And we talk with Noam Shomron, associate professor at the Sackler School of Medicine at Tel Aviv University, about technological advancements his lab has made in the genetic testing of fetuses.