Project Update - Month 18
Summary
NMD-Chip aims to help people living with NMDs gain a genetic diagnosis more quickly. New technology will enable testing for all of the mutations that we know cause NMDs simultaneously, which is a much faster and cheaper process. Secondly the project aims to discover new genes not previously known to be responsible for NMDs.
Strategy
The scientific strategy of the project is to design chips for known genes and chips for candidate genes . They will look for:
• extra bits of genetic code which shouldn’t be there (insertions)
• missing bits of code (deletions) and
• mistakes in the code (point mutations).
The technology used, developed by Roche-Nimblegen, allows up to 2.1 million mutations to be tested for on one chip. The results are read with a scanner and analysed with powerful bioinformatics software.
Progress so far
The project has now reached its half-way point and much progress has been made. This report is a brief summary of achievements at the end of 18 months.
Project Management
The NMD-Chip Kick-Off Meeting was held in Paris on November 18-19th 2008. Since then, the steering committee has met approximately every 6 months. At these meetings NMD-chip researchers have been able to collaborate, share information, discuss progress and make decisions about the project’s progress together.
Known-gene chip development
Sequences for 50 genes known to be implicated in LGMD, congenital muscular dystrophies and congenital myopathies and 43 genes implied in the CMT group of diseases were selected.
The information about these genes and sequences was included together with other information collected from the partners to create a database for chip design.
With the help of this information, two chips to test all the genes known to be involved in the NMDs under study have been developed. The first is dedicated to muscular dystrophies, congenital muscular dystrophies, and congenital myopathies. The second is dedicated to hereditary motor sensory neuropathies (Charcot-Marie-Tooth disease).
These chips have been checked (validated) using DNA samples from patients who have already had a genetic diagnosis. This has been done on 2 generations of chips and will be carried out a third generation chip which will improve on the first two prototypes. This way, the researchers know that they work – that they detect the mutations they are designed to find.
Candidate-gene chip development
The candidate-gene chips have also been designed and are currently being checked (validated). These chips aim to identify new genes involved in three groups of diseases: congenital muscular dystrophies (CMD); Charcot-Marie-Tooth diseases (CMT); and limb-girdle muscular dystrophies (LGMD).
309 candidate genes for CMT were selected, based on the scientists’ expertise, using data from the literature and bioinformatics tools.
Using similar techniques, a list of 345 functional candidate genes for CMD and 467 for LGMD have been selected.
Bioinformatics
Several software tools have been created to improve the chip design, to collect data, and to analyse the mutations detected by the chips. Partners have been adding data to the database and the entries have been checked to ensure they have been added accurately.
Website
A project website has been set up at www.nmd-chip.eu which enables dissemination of information about the project . An intranet platform has also been set up so that the partners in the project can share results and have online discussions about the project easily.
Societal aspects
A project ethics council has been established in order to advise and answer questions from NMD-CHIP partners and stakeholders. The PEC details are listed on the website along with links to relevant documentation (such as the Human Tissue Act) and other organisations dealing with bio-ethics.
