Featured Research

from universities, journals, and other organizations

Next-generation DNA sequencing to improve diagnosis for muscular dystrophy

Date:
March 5, 2012
Source:
University of Nottingham
Summary:
Scientists have used a revolutionary new DNA-reading technology for a research project that could lead to correct genetic diagnosis for muscle-wasting diseases. The technique could be used to offer people with muscular dystrophy, or a related neuromuscular condition, a more accurate prognosis, which would enable them to make more informed choices on life decisions, including family planning.

Scientists at The University of Nottingham have used a revolutionary new DNA-reading technology for a research project that could lead to correct genetic diagnosis for muscle-wasting diseases.

The technique could be used to offer people with muscular dystrophy, or a related neuromuscular condition, a more accurate prognosis, which would enable them to make more informed choices on life decisions, including family planning.

The researchers used a next-generation DNA sequencing machine to investigate the condition of a patient who had previously been misdiagnosed with the wrong type of muscular dystrophy.

The research, led by Professor Jane Hewitt in the University’s School of Biology, was funded by the Muscular Dystrophy Campaign through a PhD studentship for Andreas Leidenroth.

Andreas said: “Our case study demonstrates how genetic diagnostics will be done in the future. New DNA sequencing machines will be cheap to run, easy to use, fit on a desk and decode an entire human genome in minutes. High-throughout DNA sequencing in the NHS is no longer a question of ‘if’, but of ‘when’. The biggest challenge will be to develop standardised filtering guidelines so that we can easily extract medically relevant information from these large DNA datasets.”

The study, published in the European Journal of Human Genetics, focused on a person who had previously been diagnosed with facioscapulohumeral muscular dystrophy (FSHD) — a type of muscular dystrophy that predominantly affects muscles of the face, shoulder and upper arm. However, when the researchers studied her DNA more closely they found several inconsistencies and realised that she was highly unlikely to have FSHD.

To gain a genetic diagnosis for this, traditionally genes known to be involved in muscular dystrophies would have to be tested one by one, which can be a laborious and time consuming process. This would also have limited the search to a small number of genes and risked missing the mutation.

Instead, the Nottingham team used whole genome sequencing which, rather than reading the code of a single gene at a time, can simultaneously decipher the more than 25,000 genes of the human genome. This had the advantage of almost guaranteeing to examine the mutated gene but also poses a serious challenge: human DNA can vary from one person to the next so how could they tell which was a harmful genetic mutation rather than a harmless ‘spelling difference’ unique to that person?

The Nottingham researchers used different data filters to carefully narrow them down. First they ignored all spelling differences that had already been reported in the genomes of healthy people, assuming them to be harmless. This left 950 differences, of which 450 looked like they might be harmful mutations. When they compared this shortlist to 30 known muscular dystrophy genes, they found two matches: the patient had two mutations in a gene known to cause limb-girdle muscular dystrophy (LGMD) type 2A, correcting the genetic diagnosis of this patient.

Due to the complexities of these diseases, more than 20 per cent of all people with muscular dystrophy or a related neuromuscular condition are currently living without a genetic diagnosis, leaving around 10,000 people in the UK without accurate information about how their condition will progress. Treatments are on the horizon for many of these conditions and to access these patients will need an accurate diagnosis.

The study demonstrates the power of next generation sequencing as a diagnostic tool. While health services like the NHS are likely to adopt similar technologies in the near future, these methods are still rapidly evolving and research-based case studies such as this one will provide important guidance for other researchers and prove the feasibility of these methods.

Dr Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign said: “Diagnosing neuromuscular disorders can be extremely difficult — there are currently thousands of people in the UK living in a state of limbo with no definite answers about their condition. Not only is it psychologically difficult but it can have real consequences upon people’s lives, making decisions about treatment options and having children much harder. This research is extremely promising and will bring hope to many families.”

The Nottingham researchers worked on the DNA sequencing in collaboration with colleagues at the Norwegian High-Throughput Sequencing Centre in Oslo, which was enabled by a Nottingham Robert’s Money Building Experience and Skills Travel Scholarship (BESTS).


Story Source:

The above story is based on materials provided by University of Nottingham. Note: Materials may be edited for content and length.


Journal Reference:

  1. Andreas Leidenroth, Hanne Sørmo Sorte, Gregor Gilfillan, Melanie Ehrlich, Robert Lyle, Jane E Hewitt. Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole-exome analysis. European Journal of Human Genetics, 2012; DOI: 10.1038/ejhg.2012.42

Cite This Page:

University of Nottingham. "Next-generation DNA sequencing to improve diagnosis for muscular dystrophy." ScienceDaily. ScienceDaily, 5 March 2012. <www.sciencedaily.com/releases/2012/03/120305132319.htm>.
University of Nottingham. (2012, March 5). Next-generation DNA sequencing to improve diagnosis for muscular dystrophy. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2012/03/120305132319.htm
University of Nottingham. "Next-generation DNA sequencing to improve diagnosis for muscular dystrophy." ScienceDaily. www.sciencedaily.com/releases/2012/03/120305132319.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Artificial Sweetener Could Promote Diabetes

Artificial Sweetener Could Promote Diabetes

Newsy (Sep. 17, 2014) — Doctors once thought artificial sweeteners lacked the health risks of sugar, but a new study says they can impact blood sugar levels the same way. Video provided by Newsy
Powered by NewsLook.com
Ebola Vaccine Trial Gets Underway at Oxford University

Ebola Vaccine Trial Gets Underway at Oxford University

AFP (Sep. 17, 2014) — A healthy British volunteer is to become the first person to receive a new vaccine for the Ebola virus after US President Barack Obama called for action against the epidemic and warned it was "spiralling out of control." Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Obesity Rates Steady Even As Americans' Waistlines Expand

Obesity Rates Steady Even As Americans' Waistlines Expand

Newsy (Sep. 17, 2014) — Researchers are puzzled as to why obesity rates remain relatively stable as average waistlines continue to expand. Video provided by Newsy
Powered by NewsLook.com
President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) — President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins