Season of mists, mellow fruitfulness… ..and DNA

I always associate October with the lines of the famous poem ‘Ode to Autumn’ by John Keats, so this was a line that came into my head when I was looking for a catchy title for a blog post about the opening of the UK MND DNA Bank to the international community today.DNABankLogo

Yes, from 1 October, many peoples’ generosity, hard work and energy, has paid off, we have opened the doors for MND researchers from around the world to apply to access samples from the UK MND DNA Bank.

How did we get here?

The first blood samples were taken from people with MND, their families and their partners or spouses in 2003, initially by three nurses specifically employed on the project or by staff based at the MND Association’s care centre network, supporting the recruitment during their busy clinics.

The project was given a boost when it was adopted into the Department of Health’s Dementias and Neurodegenerative Diseases Research Network (DeNDRoN) portfolio. This support allowed a larger number people, in a broader area of the country to take part.

Clinical information in the form of a mandatory minimum dataset and a desirable extended clinical dataset was collected and checked. Typically two blood samples were collected, DNA was extracted from one and the second was sent to ECACC, within Public Health England.

DNA samples were transferred to BioBanking Solutions in the Centre for Integrated Genomic Medical Research, University of Manchester for quality control checks and to facilitate managed, long term maintenance of the collection. All of the samples are careful tracked and the quantity of DNA was checked by the sector-wide ‘gold standard’ assay of picogreen fluorescence. Samples were also run out on gels to check for fragmentation of the DNA during extraction.

At ECACC EBV-transformed lymphoblastoid cell lines were created from the second blood sample.

Use of the samples

Simultaneously while the ongoing collection of samples and the quality control checks were underway, the principal investigators and their collaborators have had access to the ‘warts and all’ / ‘raw’ samples within the DNA Bank. The studies completed so far have provided some exciting results.

In 2010, a Lancet Neurology report of a 600-sample GWAS by Aleksey Shatunov, Ammar Al-Chalabi and colleagues identified the locus (‘gene area’ or ‘postcode’) for the now-identified C9orf72 gene defect, the same analysis also hinted at / highlighted the perplexing issue of the presence of C9orf72 gene defects in small proportion of patients with sporadic MND. The use of the UK MND DNA Bank samples and the later papers by Renton et al and DeJesus-Hernandez et al identifying the C9orf72 gene as the defective gene in this locus have changed the way we think about MND, and inherited MND in particular.

A success I’m particularly pleased to see is the number of times that the data from this first GWAS study has been re-used – so already that subset of 600 pseudo-anonymsed participants’ samples have been used to tell us new things about the genetic contribution to motor neurone disease; namely about the contribution of recessive variations and exploring the possibility that there’s something else hiding in that elusive C9 postcode (for more information see Mok et al and Jones et al respectively).

Originally intended as an everlasting supply, or a back up, for the extracted DNA, an unforeseen benefit of collecting EBV-transformed cell lines, is the value of these cell lines to MND research in their own right. Cell pellet samples are currently being used in gene expression studies, with a potential for much wider use in the future.

One of the aims of the DNA Bank was to understand more about all forms of MND, exploring the contribution of genetic variations in those people with MND without a family history. In an additional study connected to the DNA Bank, the next step on from this – combining knowledge of these genetic variations with a knowledge of the environment and lifestyle of the participants – is drawing to an end. But that’s a story for another post.. !

Thank yous

The creation of the DNA Bank was truly a team effort. Firstly, thank you to all those with MND, their spouses, partners and families who gave samples to the DNA Bank. Thank you to all those who helped collect the samples (the participating centres are listed on our website) and those who’ve helped manage the samples and data. Thank you to the Wellcome Trust for funding the EBV transformations part of the project and to DeNDRoN for their support.

Right project at the right time

The UK MND DNA Bank began as an idea by the Board of Trustees of the MND Association to fund a programme grant that would make a ‘quantum difference’ or ‘a big-step forward’ in our understanding of MND. Several proposals were considered but the DNA Bank was chosen.

The reasons for making the choice was that the DNA Bank provided an opportunity for people with MND to contribute to research; it would promote collaboration among researchers, and that the time was right – gene-reading technology and the computing power to analyse the results were rapidly developing.

All of these reasons have stood the test of time. It’s a fantastic achievement that I’m very proud to be part of. I look forward to being able to report again on it’s contribution to a world free from MND.