Project MinE: unraveling genetic basis of ALS by large-scale genetic sequencing

Amyotrophic lateral sclerosis (ALS) is one of the most devastating diseases and leads to progressive muscle weakness, which leaves the patient paralyzed. As such, respiratory failure is the most common cause of death for people with ALS. ALS can strike at any adult age. There is no effective treatment.

Project MinE aims to find the genetic causes of ALS which is necessary to ultimately develop a cure. The project aims to map the DNA of at least 15,000 ALS patients and 7,500 control subjects with the innovative whole genome sequencing. Sequencing means that every letter of the 6 billion letter DNA is read. The resulting 22,500 sequenced DNA profiles will be compared.

Project MinE is an initiative of ALS patients and private and public organisations, and combines (international) fundamental research efforts in academic research institutions with innovative industry to find the cause and cure for ALS. The ALS genes identified in Project MinE are an important starting point for translational research and the search for new therapeutic compounds for biotech company Treeway. By combining strengths of different stakeholders in collaborative and integrative development, maximum effect can be obtained and best use is made of the excellent knowledge base that is available in The Netherlands. The project aims to develop a cost-effective health solution and accelerate its delivery, which fits the objectives of the Top Sector Life Sciences & Health perfectly. All project partners contribute to Project MinE in kind or in cash, and provide operational and scientific input.

The final step is the combined processing and analysis of all gathered whole genome and exome sequencing data, a phase for which the strategy is defined and led by the Dutch team, including the use of analysis results for development of a cure for ALS together with industry (this application). In summary, the project achieved the following: 

• Samples/ funding from other countries.  
• Project MinE as of December 2019 now includes 19 countries.  
• The construction of a fruitful scientific international community within Project MinE 
• Effective datasharing for external researchers  
• Collecting over 6,000 ALS genomes, 10,000 control genomes, and over 25,000 control exomes.  
• Setting up and maintaining an ICT infrastructure that allows for all of the above.

The data analysis so far within Project MinE already contributed to the discovery of ALS risk genes TUBA4A, TBK1, C21orf2, NEK1, NIPA1, KIF5A and 3 novel GWAS loci were discovered, based on the Dutch genomes. This contributes to understanding the (genetic) cause of ALS which is necessary to ultimately develop a cure.