Unique ALS ‘Exome-Sequencing’ Project Is Focus of New Grant

MDA has awarded a $400,000 grant to National Institutes of Health (NIH) Laboratory of Neurogenetics researchers to perform exome sequencing on samples taken from 1,000 people with sporadic amyotrophic lateral sclerosis (ALS). The project will be led by neurologist Bryan Traynor, head of the Neuromuscular Diseases Research Group at the NIH in Bethesda, Md.    

Data generated by the first-of-its-kind project will be made publicly available online and is expected to accelerate the pace of ALS research by helping scientists identify genes associated with the disease.

The infrastructure award was made through MDA's translational research program. In addition to MDA funding, the project will leverage resources through the Intramural Research Program at the NIH and adds value to tissue samples already available to researchers through the Coriell ALS Repository.

Exome sequencing decodes exons

Compared to previous generations of technology, exome sequencing is a faster and less expensive way to reveal the chemical “letters” that make up the human genome (DNA), and search for genes associated with human diseases.

As opposed to whole genome sequencing, in which a readout of an individual’s entire genome is produced, exome sequencing decodes only the stretches of DNA called exons, which contain instructions used in protein synthesis. (Introns, the DNA regions that do not contain information used to make proteins, are ignored.)

Although exons make up only about 1.5 percent of the genome, the vast majority of disease-causing mutations occur in these sections.

MDA-NIH project has a 12-month timeline

The exome-sequencing project, which is expected to be completed within 12 months, will produce genetic information for:

• 360 deceased individuals who had the sporadic form of ALS, for whom post-mortem tissue samples are available; and
• 640 samples stored at the Coriell ALS Repository from people (both living and deceased) with sporadic ALS.

(Only about 5 percent of ALS is familial, where there is a history of ALS in more than one family member; the other 95 percent occurs sporadically without any family history of the disease.)

Exome sequencing data from a large number of people unaffected by ALS will be used for comparison in analysis.

Identification of genes will speed ALS research

Researchers will be able to correlate much of the genetic information generated by the project with specific tissue samples that are accessible through Coriell, allowing for the seamless transitioning to many lines of further research.

Although samples will be taken from people with sporadic ALS, some will be found to have mutations in genes associated with familial ALS.

It is hoped the sequencing project also will uncover new genes that, when mutated, can cause ALS, as well as combinations of genes or genetic sequences that either increase the risk of getting the disease or modify its course.

Scientists will be able to use such data to better understand what processes are disrupted in ALS. The findings could lead to better diagnostic tests, and in turn to earlier or more precise diagnosis, and may point the way to various targets around which therapies can be developed.