Development of an information-rich assay for C9ORF72 as a test for ALS and FTD

DESCRIPTION (provided by applicant): The long term goal of this project is to develop, validate, and commercialize an assay to improve screening of C9ORF72, a gene on chromosome 9 that is linked to frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Expansions of a guanine and cytosine rich hexanucleotide repeat (GGGGCC) in the non-coding region of C9ORF72 is associated with up to 67 percent of familial ALS, making it the most prevalent genetic mutation for a disease with an annual economic burden of 433M in the US. The expansion also appears in about 25 percent of familial FTD, as well as 7 percent of sporadic ALS and 5 percent of sporadic FTD. The C9ORF72 region is difficult to size accurately because most expansions in affected individuals are more than 700 repeats in length. Currently testing relies on homebrew PCR-based assays for accurate sizing of lt35 repeats, or, separately, Southern blot analysis for crude sizing of gt35 repeats. A solution is needed to enable high throughp