Speeding Up Genetic Diagnosis of Huntington’s Disease

Summary: Researchers have developed a method to determine the length of mutated genes associated with Huntington’s disease quickly and easily.

Source: Swiss National Science Foundation.

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 dna chip
For the analysis, the team extracts the DNA from blood cells, amplifies the concerned region and determines its size with a newly developed chip. NeuroscienceNews.com image is credited to the researchers.

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.

About this neuroscience research article

Source: Vincent Dion – Swiss National Science Foundation
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to the researchers.
Original Research: Open access research for “µLAS: Sizing of expanded trinucleotide repeats with femtomolar sensitivity in less than 5 minutes” by Rémi Malbec, Bayan Chami, Lorène Aeschbach, Gustavo A. Ruiz Buendía, Marius Socol, Pierre Joseph, Thierry Leïchlé, Evgeniya Trofimenko, Aurélien Bancaud & Vincent Dion in Scientific Reports. Published January 10 2019.

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Swiss National Science Foundation “Speeding Up Genetic Diagnosis of Huntington’s Disease.” NeuroscienceNews. NeuroscienceNews, 13 January 2019.
<https://neurosciencenews.com/huntingtons-genetics-10520/>.[/cbtab][cbtab title=”APA”]Swiss National Science Foundation(2019, January 13). Speeding Up Genetic Diagnosis of Huntington’s Disease. NeuroscienceNews. Retrieved January 13, 2019 from https://neurosciencenews.com/huntingtons-genetics-10520/[/cbtab][cbtab title=”Chicago”]Swiss National Science Foundation “Speeding Up Genetic Diagnosis of Huntington’s Disease.” https://neurosciencenews.com/huntingtons-genetics-10520/ (accessed January 13, 2019).[/cbtab][/cbtabs]


µLAS: Sizing of expanded trinucleotide repeats with femtomolar sensitivity in less than 5 minutes

We present µLAS, a lab-on-chip system that concentrates, separates, and detects DNA fragments in a single module. µLAS speeds up DNA size analysis in minutes using femtomolar amounts of amplified DNA. Here we tested the relevance of µLAS for sizing expanded trinucleotide repeats, which cause over 20 different neurological and neuromuscular disorders. Because the length of trinucleotide repeats correlates with the severity of the diseases, it is crucial to be able to size repeat tract length accurately and efficiently. Expanded trinucleotide repeats are however genetically unstable and difficult to amplify. Thus, the amount of amplified material to work with is often limited, making its analysis labor-intensive. We report the detection of heterogeneous allele lengths in 8 samples from myotonic dystrophy type 1 and Huntington disease patients with up to 750 CAG/CTG repeats in five minutes or less. The high sensitivity of the method allowed us to minimize the number of amplification cycles and thus reduce amplification artefacts without compromising the detection of the expanded allele. These results suggest that µLAS can speed up routine molecular biology applications of repetitive sequences and may improve the molecular diagnostic of expanded repeat disorders.

Feel free to share this Neuroscience News.
Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.
We hate spam and only use your email to contact you about newsletters. You can cancel your subscription any time.