Project MinE is an independent large scale whole genome research project that was initiated by 2 patients with

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

and started on World ALS Day, June 21, 2013. The symptoms of

are caused by degeneration of motor nerve cells (

motor neurons A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly ...

) in the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spin ...

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is ...

, and

motor cortex The motor cortex is the region of the cerebral cortex believed to be involved in the planning, control, and execution of voluntary movements. The motor cortex is an area of the frontal lobe located in the posterior precentral gyrus immediately ...

. The exact cause of this degeneration is unknown but it is thought that environmental exposures and genetic factors play a role in susceptibility to the disease. In 5-10% of patients the family history is positive for ALS. However, it is not always possible to establish the mode of

inheritance Inheritance is the practice of receiving private property, titles, debts, entitlements, privileges, rights, and obligations upon the death of an individual. The rules of inheritance differ among societies and have changed over time. Offici ...

in each pedigree and not all familial cases may suffer from a genuine

Mendelian Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later populari ...

monogenic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

. Autosomal-dominant mutations in the

C9orf72 C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene ''C9orf72''. The human ''C9orf72'' gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,546 to base pa ...

and the

SOD1 Superoxide dismutase u-Zn'' also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the ''SOD1'' gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, fa ...

gene are found in a substantial number of familial ALS cases. Mutations in other genes (such as

VAPB Vesicle-associated membrane protein-associated protein B/C is a protein that in humans is encoded by the ''VAPB'' gene. The VAPB gene is found on the 20th human chromosome. Together with VAPA, it forms the VAP protein family. Function The p ...

ANG,

TARDBP TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by the ''TARDBP'' gene. Structure TDP-43 is 414 amino acid residues long. It consists of 4 domains: an N-terminal d ...

and FUS) have been reported, but are found at a much lower frequency and with variable penetrance, suggesting the involvement of other genes. Project MinE is a research project to systematically interrogate the

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the ...

for both common and rare genetic variation in ALS (genetic "data mining" explains the project name). The project consists of two phases and combines a

genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any varian ...

(GWAS) study with

whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...

: * Phase 1 of Project MinE consists of whole genome sequencing of 300 DNA samples of ALS patients to detect relevant haplotypes with high fidelity (variant calling &

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...

detection). Subsequently, expansion of the current GWAS for ALS will take place by increasing the amount of DNA samples to be investigated to 15,000 ALS samples and 20,000 healthy controls (so 35,000 samples in total) and imputation using the whole genome sequencing results will be performed. Combining these two processes will result that a relatively small group of whole genome sequenced DNA samples will extend the > 500,000 single nucleotide polymorphism (SNP) markers of a GWAS to 8,000,000 SNP markers and per definition will include ALS-relevant variation. * Phase 2 of the project aims to increase the number of whole genome sequenced samples to 22,500, which includes 15,000 ALS samples and 7,500 healthy controls. High-throughput

next-generation sequencing Massive parallel sequencing or massively parallel sequencing is any of several high-throughput approaches to DNA sequencing using the concept of massively parallel processing; it is also called next-generation sequencing (NGS) or second-generation s ...

will be applied. This sample size will be large enough to reliably analyze whole genome sequencing data outside of a family context. The long-term benefit of the approach taken for project MinE is the priceless catalogue of many non-ALS whole genomes that can be used to investigate other human diseases, including Diabetes Mellitus, some types of cancer, and other

neurological disorder A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...

s. Project MinE is worldwide the largest genetic study for Amyotrophic Lateral Sclerosis. The work has started in the second quarter of 2013 and is a unique international collaboration between scientists, industry, social foundations and patients. On July 25, 2016, the first results were published in 2 publications in

Nature Genetics ''Nature Genetics'' is a peer-reviewed scientific journal published by Nature Portfolio. It was established in 1992. It covers research in genetics. The chief editor is Tiago Faial. The journal encompasses genetic and functional genomic studies o ...

leading to the discovery of

NEK1 NIMA (never in mitosis gene a)-related kinase 1, also known as NEK1, is a human gene highly expressed in germ cells and thought to be involved in meiosis. It is also involved in the response to DNA damage from radiation; defects in this gene can b ...

and C21orf2 as new ALS risk genes.

References

External links

* {{Official website, http://www.projectmine.com * http://www.genome.gov/GWAStudies Genome projects