ALS Genes in the Genomic Era and their Implications for FTD

Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Hung Phuoc Nguyen, Christine Van Broeckhoven, Julie van der ZeeAmyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient–control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology. As more causal and risk genes are identified, it has become apparent that affected individuals can carry multiple disease-associated variants. In light of this observation, we discuss the oligogenic architecture of ALS. To end, we highlight emerging key molecular processes and opportunities for therapy.

Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research