The Ice Bucket Challenge – How Did It Contribute to Scientific Research?

The Ice That Got the Gene

Remember the ice bucket challenge? Of summer 2014? Where what seemed like a lot of people all of a sudden had the urge to chuck ice cold water over themselves and film it? Well it turned out this wasn’t just another new crazy internet fad. The ice bucket challenge was started by Nancy Frates from the UK after her son was diagnosed with the condition ALS (amyotrophic lateral sclerosis); it was to gain awareness of the progressive neurodegenerative disease and raise money to fund new research. There were over 17million people who uploaded videos of their challenge onto social media sites including many celebrities such as Bill Gates and Mark Zuckerberg. A staggering £87.7M was raised for ALS, funding 6 new research projects! This has led to the scientific discovery of new genes associated with both the hereditary and sporadic causes of the disease that will lead to new therapeutic targets for potential drugs.

Project MinE

Project MinE largely funded by the ice bucket challenge is the largest ever study of inherited ALS. More than 80 researchers from over 11 different countries conducted searches for risk genes in ALS affected families. Bernard Muller and Robert Jan Suit, entrepreneurs from the Netherlands, were both diagnosed with ALS in 2010 and 2011. They made a decision to turn their business skills to finding a solution and so founded Project MinE. The project started with thousands of untested blood samples from ALS patients that were sat gathering dust in a Netherlands lab. Project MinE was chosen to be the recipient of the funds raised by the ice bucket challenge which enabled them to fund their project and commence the analysis of the blood samples. The researchers used arrays of common single nucleotide polymorphisms (SNPs) to genotype 15,156 ALS patients and 26,224 healthy controls from many different countries totalling more than 18 million SNPs tested. Some 1,861 had whole genome sequencing, which involves reading every single one of the six billion letters in the human genome (A, G, C, T).

What is a Single Nucleotide Polymorphism?

A nucleotide is a single building block of DNA. There are 4 building blocks of DNA: adenine (A), guanine (G), cytosine (C), thymine (T). A single nucleotide polymorphism is the most common form of variation in the genetic code and involves the change of one nucleotide. For example, in a certain segment of DNA a SNP may replace adenine with cytosine. These changes occur once in every 300 nucleotides throughout the genome averaging around 10 million SNPs. These nucleotide changes can affect a genes function, but most have no effect on a person’s health or development. SNPs can be used by scientists to discover information within the genome such as being a biological marker allowing scientists to locate genes associated with disease. They can be used to track disease inheritance, predict a person’s response to certain drugs, and susceptibility to toxins.

 

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New Risk Gene

A new risk gene now associated with and believed to be in amongst the most common genes to contribute to ALS is the NEK1 gene. This gene encodes for the… wait for it, it’s a bit of a mouthful: serine/threonine kinase NIMA (never in mitosis gene A)- related kinase. The NEK1 gene has many diverse functions within a cell such as mitosis (production of identical daughter cells from cell division), microtubule stability, internal transportation of proteins, formation of primary cilia that sense mechanical and chemical stimuli, regulation of the permeability of the mitochondrial membrane, and assists with DNA repair. Disruption of these cellular functions is linked to the onset of ALS. The role of NEK1 in ALS is not fully understood yet; according to Dr Lucie Bruijn from the ALS Association, they are unsure whether it is the NEK1 gene itself that is connected to ALS development or mutations within the gene, with another possibility being a link between this gene combined with mutations in another gene. Including the NEK1 gene there is a total of 7 genes recently found in association with ALS which are TBK1, CCNF, GLE1, MATR3, TUBA4A, CHCHD10. This discovery has provided researchers with a new target for therapy development and a new avenue of research to look down to gain a better understanding of what causes the disease. So to all of you who participated – bravo!

Author: Laura Ellis

Editor: Molly Campbell

References

Bettencourt, C. and Houlden, H. (2015). Exome sequencing uncovers hidden pathways in familial and sporadic ALS. Nature Neuroscience, 18(5), pp.611-613.

Cirulli, E., Lasseigne, B., Petrovski, S., Sapp, P., Dion, P., Leblond, C., Couthouis, J., Lu, Y., Wang, Q., Krueger, B., Ren, Z., Keebler, J., Han, Y., Levy, S., Boone, B., Wimbish, J., Waite, L., Jones, A., Carulli, J., Day-Williams, A., Staropoli, J., Xin, W., Chesi, A., Raphael, A., McKenna-Yasek, D., Cady, J., Vianney de Jong, J., Kenna, K., Smith, B., Topp, S., Miller, J., Gkazi, A., Al-Chalabi, A., van den Berg, L., Veldink, J., Silani, V., Ticozzi, N., Shaw, C., Baloh, R., Appel, S., Simpson, E., Lagier-Tourenne, C., Pulst, S., Gibson, S., Trojanowski, J., Elman, L., McCluskey, L., Grossman, M., Shneider, N., Chung, W., Ravits, J., Glass, J., Sims, K., Van Deerlin, V., Maniatis, T., Hayes, S., Ordureau, A., Swarup, S., Landers, J., Baas, F., Allen, A., Bedlack, R., Harper, J., Gitler, A., Rouleau, G., Brown, R., Harms, M., Cooper, G., Harris, T., Myers, R. and Goldstein, D. (2015). Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science, 347(6229), pp.1436-1441.

ALSA.org. (2016). Homepage – ALS Association. [online] Available at: http://www.alsa.org/ [Accessed 19 Sep. 2016].

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